Amyotrophi c lateral s c lerosis(ALS)and frontotemporal dementia(FTD)are two closely related disorders with overlapping clinical,genetic,and neuropathological features,forming a continuous disease spectrum(Ling et al....Amyotrophi c lateral s c lerosis(ALS)and frontotemporal dementia(FTD)are two closely related disorders with overlapping clinical,genetic,and neuropathological features,forming a continuous disease spectrum(Ling et al.,2013).The major pathological hallmark of ALS and FTD are the depletion from the nucleus of the RNA-binding proteins TAR DNA‐binding protein 43(TDP-43)and FUsed in Sarcoma(FUS)and their abnormal accumulation in ubiquitin-positive cytoplasmic inclusions(Ling et al.,2013).展开更多
BACKGROUND Immature ovarian teratoma is a rare and aggressive neoplasm that affects young women.This report is the first to describe the development of immature teratoma after ovarian cystectomy for mature teratoma of...BACKGROUND Immature ovarian teratoma is a rare and aggressive neoplasm that affects young women.This report is the first to describe the development of immature teratoma after ovarian cystectomy for mature teratoma of the ovary in an adolescent female with a family history of ovarian teratoma.CASE SUMMARY A 16-year-old girl who had undergone bilateral ovarian cystectomy for mature teratomas 3 years ago showed bilateral adnexal tumors during her regular ultrasonography follow-up every 6 months.She received laparoscopic bilateral ovarian cystectomy,and final histopathology showed grade-1 immature teratoma of the left ovary and mature teratoma of the right ovary.Laparoscopic left salpingo-oophorectomy and staging procedures were performed again.Her mother,maternal aunt,and maternal grandmother had also received surgeries for mature ovarian teratomas.CONCLUSION It is important to have guidance on management of patient and family members with familial ovarian teratomas.展开更多
Familial adenomatous polyposis(FAP)is an autosomal dominant disease with a high probability of becoming cancerous.Many RNAs potentially associated with FAP have not been identified.In this study,a circRNA(circular RNA...Familial adenomatous polyposis(FAP)is an autosomal dominant disease with a high probability of becoming cancerous.Many RNAs potentially associated with FAP have not been identified.In this study,a circRNA(circular RNA)expression profile of FAP was established using a circRNA microarray,and differentially expressed circRNAs were verified by RT-qPCR.The effects of hsa_circ_0036740 on the malignant behavior of tumor cells(proliferation,apoptosis,and epithelial mesenchymal transition)and the levels of C3A complement protein expression were evaluated.Moreover,neutrophils were isolated and co-cultured with colorectal cancer cells(CRCs),followed by measurements of MPO-DNA,citrullinated histone H3,interleukin(IL)-1β,IL-6,and IL-8 levels.Nuclear translocation of arginine deiminase 4(PAD4)was observed using immunofluorescence assays.Based on the high-throughput assay,238 downregulated circRNAs,and 38 upregulated circRNAs were identified.A Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that immune regulation might be involved in FAP.A total of 10 DECs(differentially expressed circular RNAs)were identified by RT-qPCR,and among them,hsa_circ_0036740 showed the highest fold-change in upregulation.Results of gain-of-and loss-of-function studies revealed that hsa_circ_0036740 enhanced the malignant behavior of tumor cells,such as metastasis,proliferation,and apoptosis,with an increasing level of C3A complement.Moreover,hsa_circ_0036740 also significantly increased neutrophil extracellular trap formation and inflammation in neutrophils,as shown by an increased expression of PAD4.In conclusion,this study revealed the expression profiles of circRNAs in FAP and confirmed the possible involvement of hsa_circ_0036740 in the immune regulation mediated by neutrophils.Finally,hsa_circ_0036740 was suggested as a new therapeutic target for CRC.展开更多
AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was i...AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was included in the study.Whole-exome sequencing(WES)was initially used to locate copy number variations(CNVs)on 7q31.31-31.32,but failed to detect the precise breakpoint.The long-read sequencing,Oxford Nanopore sequencing Technology(ONT)was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction(QPCR)and Sanger Sequencing.RESULTS:The proband,along with her father and younger brother,were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32,which included the FEVRrelated gene TSPAN12.The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del.The proband exhibited a phase 2A FEVR phenotype,characterized by a falciform retinal fold,macular dragging,and peripheral neovascularization with leaking of fluorescence.These symptoms led to a significant decrease in visual acuity in both eyes.On the other hand,the affected father and younger brother showed a milder phenotype.CONCLUSION:The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype.The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders.展开更多
AIM:To identify and analyze the genotype of the patients with special ocular manifestations of familial vitreous amyloidosis(FVA)in a Chinese Han family.METHODS:Pars plana vitrectomy(PPV)surgery was performed on a 52-...AIM:To identify and analyze the genotype of the patients with special ocular manifestations of familial vitreous amyloidosis(FVA)in a Chinese Han family.METHODS:Pars plana vitrectomy(PPV)surgery was performed on a 52-year-old Chinese woman presented with vitreous amyloidosis and progressive visual impairment,without evidence of cardiac,renal,gastrointestinal,central nervous system or peripheral nervous system dysfunction.During the surgery,the patient presented with a gray-white dense and thick cotton woollike change in the vitreous body,accompanied by complete retinal detachment.Additionally,hard,free and movable yellow-white deposits were observed in the posterior pole and surrounding retina,the vitreous and subretinal deposits were examined by Congo red staining and immunohistochemical pathological examination,and whole exome sequencing was performed on blood samples from the patient and her cousin.RESULTS:During the operation,it was discovered that there was a complete detachment of the retina and a significant amount of hard,free-floating yellow-white deposits were observed beneath the posterior pole and surrounding retina.This is an exceedingly rare ocular manifestation.Pathological examination of the vitreous and subretinal deposit specimens revealed positive Congo red staining,as well as elevated vascular endothelial growth factor(VEGF)expression in vascular endothelial cells within the sediment specimens upon immunohistochemical examination.The patient and her cousin both exhibited a heterozygous mutation in Glyl03Arg within the transthyretin(TTR)gene,resulting in a substitution of glycine(Gly)at position 103 with arginine(Arg).CONCLUSION:FVA may present with various ocular manifestations,but panretinal detachment is a rare occurrence.In cases where retinal detachment persists for an extended period of time,amyloid deposits may form under the retina through retinal tears,leading to subretinal deposits that can impede retinal reattachment and negatively impact visual prognosis.Elevated levels of VEGF in the eyes of FVA patients may indicate an overexpression state,necessitating careful postoperative follow-up.The heterozygous mutation Gly103Arg may represent a unique pathogenic site in Chinese individuals.展开更多
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease deadly. In Africa, little data exists on this condition and the form familial is the most common with a younger age of onset. Our observations relate ...Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease deadly. In Africa, little data exists on this condition and the form familial is the most common with a younger age of onset. Our observations relate to three brothers, born from a consanguineous marriage. The diagnosis of amyotrophic lateral sclerosis was certain placed in all patients according to the criteria of Awaji. The average age of patients was 16.66 years, and the average age of onset of symptoms was 10.33 years old. The female gender was the most represented with a sex ratio of 0.5. Our patients benefited from rilusole, vitamin D and physiotherapy. A only patient presented with dysphagia. However, no cases have been observed at this day.展开更多
Objectives: It is to determine the prevalence of familial hypercholesterolemia (FH) among adult Filipino patients with dyslipidemia at Universidad de Santa Isabel Health Services Department in one year. Methods: An ob...Objectives: It is to determine the prevalence of familial hypercholesterolemia (FH) among adult Filipino patients with dyslipidemia at Universidad de Santa Isabel Health Services Department in one year. Methods: An observational descriptive prospective study involves Filipino patients, aged 19 years and older, with dyslipidemia. The Dutch Lipid Network (DLN) Criteria was used to diagnose FH. Prevalence data and categorical variables were expressed as percentages, while continuous variables were reported as mean and standard deviations. Results: 529 patients were included in the study. 302 were females, and 227 were males. 180 (34%) scored Unlikely, 100 (19%) scored Probable, 185 (35%) scored Possible, and 64 (12%) were classified under Definite Familial Hypercholesterolemia. Most of the patients diagnosed with definite FH did not have diabetes, cerebrovascular disease (CVD), and coronary artery disease (CAD). The diagnosis was not affected by gender, BMI, smoking, and alcohol consumption. Hypertension was significantly correlated to the diagnosis of FH, as most of them were already hypertensive at diagnosis. It was noted that hypertension, diabetes, CVD, and CAD were seen at an earlier age among patients with definite FH. Conclusion: The prevalence of heterozygous FH at 12% among dyslipidemia patients and 1.3% among the general population was described for the first time in our region. This result should raise the awareness of our healthcare providers that FH, which is a major risk factor for premature CAD and CVD, exists, and early detection and management are important.展开更多
In this paper we present a five-generation kindred with familial eosinophilia, associated with valvular heart disease in one of seven members of the second generation, four of sixteen members of the third generation, ...In this paper we present a five-generation kindred with familial eosinophilia, associated with valvular heart disease in one of seven members of the second generation, four of sixteen members of the third generation, four of thirty-one members of the fourth generation, and two of twenty members of the fifth generation;the clinical features of the two members of the first generation are unavailable. Of a total of 48 members, 26 had eosinophilia, with counts ranging from 1761 to 6045 cells/mm<sup>3</sup>, with apparent autosomal dominant propagation;this confirms the experience of the authors of previous studies on this condition. Genetic analysis on eight members, which we reported in an earlier paper [1], revealed a pericentric inversion of chromosome 10 in two members. The entity of Familial Eosinophilia has been generally considered benign. However, the clinical presentation of this kindred was unusual in that valvular and endocardial damage, was frequent findings, without apparent involvement of the other organs and tissues. Mitral valve damage leading to both stenosis and regurgitation and requiring mitral valve replacement was noted in the index patient. This unique presentation may suggest that in patients with mitral valve disease, if blood eosinophilia is noted, it could point to a non-rheumatic etiology, thus a possible opportunity for treatment to prevent further damage to the heart. This recommendation may be even more timely, as many effective treatments are now available to treat even high-grade hypereosinophilia.展开更多
Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretio...Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretion,and/or caused by defects in the secretory machinery of cholangiocytes.Several mutations and pathways that lead to cholestasis have been described.Progressive familial intrahepatic cholestasis(PFIC)is a group of rare diseases caused by autosomal recessive mutations in the genes that encode proteins expressed mainly in the apical membrane of the hepatocytes.PFIC 1,also known as Byler’s disease,is caused by mutations of the ATP8B1 gene,which encodes the familial intrahepatic cholestasis 1 protein.PFIC 2 is characterized by the downregulation or absence of functional bile salt export pump(BSEP)expression via variations in the ABCB11 gene.Mutations of the ABCB4 gene result in lower expression of the multidrug resistance class 3 glycoprotein,leading to the third type of PFIC.Newer variations of this disease have been described.Loss of function of the tight junction protein 2 protein results in PFIC 4,while mutations of the NR1H4 gene,which encodes farnesoid X receptor,an important transcription factor for bile formation,cause PFIC 5.A recently described type of PFIC is associated with a mutation in the MYO5B gene,important for the trafficking of BSEP and hepatocyte membrane polarization.In this review,we provide a brief overview of the molecular mechanisms and clinical features associated with each type of PFIC based on peer reviewed journals published between 1993 and 2020.展开更多
In order to compare the clinical characteristics of familial and non-familial bullous lichen planus (BLP), the archival data of 36 BLP patients with positive family history and 21 BLP patients with negative family his...In order to compare the clinical characteristics of familial and non-familial bullous lichen planus (BLP), the archival data of 36 BLP patients with positive family history and 21 BLP patients with negative family history diagnosed according to the clinical features and histopathology were collected in our department from 1956 to 2003. The clinical features were analyzed and compared. There were significant differences between familial and non-familial BLP in age of onset, duration of disease and extension of eruption (P<0.01). It was concluded that familial BLP appeared to differ from the non-familial form in its earlier age of onset, longer duration of the disease, more extensive eruption and more tendency to involve nails. Hereditary factors may play a role in the pathogenesis of familial BLP.展开更多
BACKGROUND:Three types of progressive familial intrahepatic cholestasis(PFIC)have been identified,but their etiologies include unknown mechanisms. DATA SOURCES:A PubMed search on"progressive familial intrahepatic...BACKGROUND:Three types of progressive familial intrahepatic cholestasis(PFIC)have been identified,but their etiologies include unknown mechanisms. DATA SOURCES:A PubMed search on"progressive familial intrahepatic cholestasis"and"PFIC"was performed on the topic,and the relevant articles were reviewed. RESULTS:The etiologies of the three PFIC types still include unknown mechanisms.Especially in PFIC type 1,enterohepatic circulation of bile acid should be considered.Ursodeoxycholic acid,partial external biliary diversion and liver transplantation have been used for the treatment of PFIC patients according to disease course. CONCLUSIONS:Since the etiologies and disease mechanisms of PFIC are still unclear,detailed studies are urgently required. Strategies for more advanced therapies are also needed.These developments in the future are indispensable,especially for PFIC type 1 patients.展开更多
Genotyping is conclusive for the diagnosis of progressive familial intrahepatic cholestasis type 3(PFIC3). Here we report a Chinese patient of PFIC3 with compound mutations in the ABCB4 gene. Liver biopsy was performe...Genotyping is conclusive for the diagnosis of progressive familial intrahepatic cholestasis type 3(PFIC3). Here we report a Chinese patient of PFIC3 with compound mutations in the ABCB4 gene. Liver biopsy was performed on a 17-year-old male patient with intrahepatic cholestasis of unknown etiology. Liver histology findings are indicative of intrahepatic cholestasis with extensive fibrosis. Genotyping revealed c.175C>T(p.L59L) mutation in exon 4, c.504C>T(p.N168N) mutation in exon 6, c.711A>T(p.I237I) mutation in exon 8, c.874A>T(p.K292X) in exon 9 and a novel mutation, c.1804G>T(p.G602W) in exon 15. Based on these findings, the patient was diagnosed with PFIC3. The novel mutation p.G602 W in exon 15 was predicted as probably damaging by Poly Phen-2 with a score of 0.986(sensitivity: 0.54; specificity: 0.94) and was predicted to affect protein function with a SIFT score of 0.01.展开更多
BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resul...BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resulting in a hepatocellular form of cholestasis.While the diagnosis of such disorders had historically been based on pattern recognition of unremitting cholestasis without other identified molecular or anatomic cause,recent scientific advancements have uncovered multiple specific responsible proteins.The variety of identified defects has resulted in an ever-broadening phenotypic spectrum,ranging from traditional benign recurrent jaundice to progressive cholestasis and end-stage liver disease.AIM To review current data on defects in bile acid homeostasis,explore the expanding knowledge base of genetic based diseases in this field,and report disease characteristics and management.METHODS We conducted a systemic review according to PRISMA guidelines.We performed a Medline/PubMed search in February-March 2019 for relevant articles relating to the understanding,diagnosis,and management of bile acid homeostasis with a focus on the family of diseases collectively known as PFIC.English only articles were accessed in full.The manual search included references of retrieved articles.We extracted data on disease characteristics,associations with other diseases,and treatment.Data was summarized and presented in text,figure,and table format.RESULTS Genetic-based liver disease resulting in the inability to properly form and secrete bile constitute an important cause of morbidity and mortality in children and increasingly in adults.A growing number of PFIC have been described based on an expanded understanding of biliary transport mechanism defects and the development of a common phenotype.CONCLUSION We present a summary of current advances made in a number of areas relevant to both the classically described FIC1(ATP8B1),BSEP(ABCB11),and MDR3(ABCB4)transporter deficiencies,as well as more recently described gene mutations--TJP2(TJP2),FXR(NR1H4),MYO5B(MYO5B),and others which expand the etiology and understanding of PFIC-related cholestatic diseases and bile transport.展开更多
AIM:To study the characteristics of APC(adenomatous polyposis coli)gene germline mutation in Chinese patients with familial adenomatous polyposis(FAP).METHODS:APC gene from 14 FAP families was amplified by polymerase ...AIM:To study the characteristics of APC(adenomatous polyposis coli)gene germline mutation in Chinese patients with familial adenomatous polyposis(FAP).METHODS:APC gene from 14 FAP families was amplified by polymerase chain reaction(PCR)and underwent direct sequencing to determine the micromutation type.For the samples without micromutation,the large fragment deletion of APC gene was examined by multiplex ligation-dependent probe amplification(MLPA).RESULTS:There were gene micromutations in 9 families with a micromutation detection rate of 64.3%(9/14),including 6 frameshift mutations(66.7%),1 nonsense mutation(11.1%)and 2 splicing mutations(22.2%).Large fragment deletions were detected by MLPA in 2 families.The total mutation detection rate of micromutations and large fragment deletions was 78.6%(11/14).CONCLUSION:The detection rate of APC gene germline mutation can be improved by direct sequencing combined with MLPA large fragment deletion detection.展开更多
Familial adenomatous polyposis(FAP) is an autosomal dominant inherited syndrome characterized by multiple adenomatous polyps(predisposing to colorectal cancer development) and numerous extracolonic manifestations. The...Familial adenomatous polyposis(FAP) is an autosomal dominant inherited syndrome characterized by multiple adenomatous polyps(predisposing to colorectal cancer development) and numerous extracolonic manifestations. The underlying genetic burden generates variable clinical features that may influence operative management. As a precancerous hereditary condition, the rationale of performing a prophylactic surgery is a mainstay of FAP management. The purpose of the present paper is to bring up many controversial aspects regarding surgical treatment for FAP, and to discuss the results and perspectives of the operative choices and approaches. Preferably, the decision-making process should not be limited to the conventional confrontation of pros and cons of ileorectal anastomosis or restorative proctocolectomy. A wide discussion with the patient may evaluate issues such as age, genotype, family history, sphincter function, the presence or risk of desmoid disease, potential complications of each procedure and chances of postoperative surveillance. Therefore, the definition of the best moment and the choice of appropriate procedure constitute an individual decision that must take into consideration patient's preferences and full information about the complex nature of the disease. All these facts reinforce the idea that FAP patients should be managed by experienced surgeons working in specialized centers to achieve the best immediate and long-term results.展开更多
Rhabdomyolysis continues to appear with increasing frequency and represents a medical emergency requiring rapid appropriate treatment. One of the unusual causes of nontraumatic rhabdomyolysis is hypokalemic periodic p...Rhabdomyolysis continues to appear with increasing frequency and represents a medical emergency requiring rapid appropriate treatment. One of the unusual causes of nontraumatic rhabdomyolysis is hypokalemic periodic paralysis without secondary causes. Primary hypokalemic periodic paralysis is a rare genetic disease characterized by episodic attacks of muscle weakness due to decreases in serum potassium. A 30-year-old woman who had 3 episodic attacks of hypokalemic periodic paralysis was admitted in emergency room with sudden onset symmetrical muscle weakness. After several hours, she started to complain myalgia and severe ache in both calves without any changes. Laboratory test showed markedly elevated creatine phosphokinase, lactic dehydrogenase levels with hypokalemia, rhabdomyolysis resulting from hypokalemia was diagnosed. Here, we report an unusual case of rhabdomyolysis caused by severe hypokalemia, which was suggested a result of familial hypokalemic periodic paralysis.展开更多
Patients with familial adenomatous polyposis(FAP),an autosomal dominant hereditary colorectal cancer syndrome,have a lifetime risk of developing cancer of nearly 100%.Recent studies have pointed out that the gut micro...Patients with familial adenomatous polyposis(FAP),an autosomal dominant hereditary colorectal cancer syndrome,have a lifetime risk of developing cancer of nearly 100%.Recent studies have pointed out that the gut microbiota could play a crucial role in the development of colorectal adenomas and the consequent progression to colorectal cancer.Some gut bacteria,such as Fusobacterium nucleatum,Escherichia coli,Clostridium difficile,Peptostreptococcus,and enterotoxigenic Bacteroides fragilis,could be implicated in colorectal carcinogenesis through different mechanisms,including the maintenance of a chronic inflammatory state,production of bioactive tumorigenic metabolites,and DNA damage.Studies using the adenomatous polyposis coliMin/+mouse model,which resembles FAP in most respects,have shown that specific changes in the intestinal microbial community could influence a multistep progression,the intestinal“adenoma-carcinoma sequence”,which involves mucosal barrier injury,low-grade inflammation,activation of the Wnt pathway.Therefore,modulation of gut microbiota might represent a novel therapeutic target for patients with FAP.Administration of probiotics,prebiotics,antibiotics,and nonsteroidal anti-inflammatory drugs could potentially prevent the progression of the adenoma-carcinoma sequence in FAP.The aim of this review was to summarize the best available knowledge on the role of gut microbiota in colorectal carcinogenesis in patients with FAP.展开更多
Restorative proctocolectomy is the most common surgical option for patients with familial adenomatous polyposis(FAP). However,adenomas may develop in the ileal pouch mucosa over time,and even carcinoma in the pouch ha...Restorative proctocolectomy is the most common surgical option for patients with familial adenomatous polyposis(FAP). However,adenomas may develop in the ileal pouch mucosa over time,and even carcinoma in the pouch has been reported. We therefore reviewed the prevalence,nature,and treatment of adenomas and carcinoma that develop after proctocolectomy in the ileal pouch mucosa in patients with FAP. In 25 reports that were reviewed,the incidence of adenomas in the ileal pouch varied from 6.7% to 73.9%. Several potential factors that favor the development of pouch polyposis have been investigated,but many remain controversial. Nevertheless,it seems certain that the age of the pouch is important. The risk appears to be 7%to 16% after 5 years,35% to 42% after 10 years,and75% after 15 years. On the other hand,only 21 cases of ileal pouch carcinoma have been recorded in the literature to date. The diagnosis of pouch carcinoma was made between 3 to 20 years(median,10 years) after pouch construction. Although the risk of malignant transformation in ileal pouches is probably low,it is not negligible,and the long-term risk cannot presently be well quantified. Regular endoscopic surveillance,especially using chromoendoscopy,is recommended.展开更多
BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)encompasses a group of autosomal recessive disorders with high morbidity and mortality.Variants in the gene encoding tight junction protein-2(TJP2)have bee...BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)encompasses a group of autosomal recessive disorders with high morbidity and mortality.Variants in the gene encoding tight junction protein-2(TJP2)have been linked to PFIC type 4(PFIC4),which predominantly presents in childhood.However,there are only limited data from adults with TJP2-related PFIC4.We report a family with an autosomal recessive disorder with a novel variant in the TJP2 gene in adults with very variable expression of PFIC4.CASE SUMMARY The index patient presented at 19 years old with liver cirrhosis and variceal bleeding and was treated with endoscopic banding and beta-blockers.In 2018,he developed primary liver cancer that was treated with radiofrequency ablation followed by liver transplantation in 2019.Genetic testing revealed a novel homozygous TJP2 variant causing PFIC4(TJP2([NM_004817.3]:c.[3334C>T];[3334C>T])).The consanguineous family consists of the father and mother(both heterozygous)and their 12 children,of which five carry the variant in a homozygous state;however,these five siblings have highly variable expression of PFIC4.Two homozygous brothers had cirrhosis and portal hypertension at diagnosis at the ages of 19 and 36.Two other homozygous brothers,age 23 and 19,and the homozygous sister,age 21,have elevated liver enzymes but presently no cirrhosis,which may suggest an age-dependent penetrance.In addition,five sisters had severe and mild intrahepatic cholestasis of pregnancy and carry the TJP2 variant in a homozygous and heterozygous state,respectively.CONCLUSION This novel TJP2 variant is associated with PFIC4 causing severe liver disease with cirrhosis and primary liver cancer in adolescents/adults.展开更多
Progressive familial intrahepatic cholestasis type 3 is caused by a mutation in the ATP-binding cassette, subfamily B, member 4 (ABCB4) gene encoding multidrug resistance protein 3. A 32-year-old woman with a history ...Progressive familial intrahepatic cholestasis type 3 is caused by a mutation in the ATP-binding cassette, subfamily B, member 4 (ABCB4) gene encoding multidrug resistance protein 3. A 32-year-old woman with a history of acute hepatitis at age 9 years was found to have jaundice during pregnancy in 2008, and was diagnosed as having intrahepatic cholestasis of pregnancy. In 2009, she underwent cholecystectomy for gallstones and chronic cholecystitis. However, itching and jaundice did not resolve postoperatively. She was admitted to our hospital with fatigue, jaundice, and a recently elevated γ-glutamyl transpeptidase level. Liver biopsy led to the diagnosis of biliary cirrhosis with ductopenia. Genetic testing revealed a pathogenic heterozygous mutation, ex13 c.1531G > A (p.A511 T), in the ABCB4 gene. Her father did not carry the mutation, but her mother's brother carried the heterozygous mutation. We made a definitivediagnosis of familial intrahepatic cholestasis type 3. He symptoms and liver function improved after 3 mo o treatment with ursodeoxycholic acid.展开更多
基金supported by AriSLA Foundation(MLOpathy and SUMOsolvable)Banca d’Italia+2 种基金German Research Foundation(DFGWE 1406/16-1)ALS Stichting grant“The Dutch ALS Tissue Bank”(to SC)。
文摘Amyotrophi c lateral s c lerosis(ALS)and frontotemporal dementia(FTD)are two closely related disorders with overlapping clinical,genetic,and neuropathological features,forming a continuous disease spectrum(Ling et al.,2013).The major pathological hallmark of ALS and FTD are the depletion from the nucleus of the RNA-binding proteins TAR DNA‐binding protein 43(TDP-43)and FUsed in Sarcoma(FUS)and their abnormal accumulation in ubiquitin-positive cytoplasmic inclusions(Ling et al.,2013).
文摘BACKGROUND Immature ovarian teratoma is a rare and aggressive neoplasm that affects young women.This report is the first to describe the development of immature teratoma after ovarian cystectomy for mature teratoma of the ovary in an adolescent female with a family history of ovarian teratoma.CASE SUMMARY A 16-year-old girl who had undergone bilateral ovarian cystectomy for mature teratomas 3 years ago showed bilateral adnexal tumors during her regular ultrasonography follow-up every 6 months.She received laparoscopic bilateral ovarian cystectomy,and final histopathology showed grade-1 immature teratoma of the left ovary and mature teratoma of the right ovary.Laparoscopic left salpingo-oophorectomy and staging procedures were performed again.Her mother,maternal aunt,and maternal grandmother had also received surgeries for mature ovarian teratomas.CONCLUSION It is important to have guidance on management of patient and family members with familial ovarian teratomas.
基金supported by The Scientific Research Cultivation Project of Meizhou People’s Hospital(No.PY-C2019001).
文摘Familial adenomatous polyposis(FAP)is an autosomal dominant disease with a high probability of becoming cancerous.Many RNAs potentially associated with FAP have not been identified.In this study,a circRNA(circular RNA)expression profile of FAP was established using a circRNA microarray,and differentially expressed circRNAs were verified by RT-qPCR.The effects of hsa_circ_0036740 on the malignant behavior of tumor cells(proliferation,apoptosis,and epithelial mesenchymal transition)and the levels of C3A complement protein expression were evaluated.Moreover,neutrophils were isolated and co-cultured with colorectal cancer cells(CRCs),followed by measurements of MPO-DNA,citrullinated histone H3,interleukin(IL)-1β,IL-6,and IL-8 levels.Nuclear translocation of arginine deiminase 4(PAD4)was observed using immunofluorescence assays.Based on the high-throughput assay,238 downregulated circRNAs,and 38 upregulated circRNAs were identified.A Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that immune regulation might be involved in FAP.A total of 10 DECs(differentially expressed circular RNAs)were identified by RT-qPCR,and among them,hsa_circ_0036740 showed the highest fold-change in upregulation.Results of gain-of-and loss-of-function studies revealed that hsa_circ_0036740 enhanced the malignant behavior of tumor cells,such as metastasis,proliferation,and apoptosis,with an increasing level of C3A complement.Moreover,hsa_circ_0036740 also significantly increased neutrophil extracellular trap formation and inflammation in neutrophils,as shown by an increased expression of PAD4.In conclusion,this study revealed the expression profiles of circRNAs in FAP and confirmed the possible involvement of hsa_circ_0036740 in the immune regulation mediated by neutrophils.Finally,hsa_circ_0036740 was suggested as a new therapeutic target for CRC.
基金Supported by the National Natural Science Foundation of China(No.82060183)Ningxia Natural Science Foundation(No.2022AAC03388)the Key Research and Development Project of Ningxia Hui Autonomous Region(No.2021BEG02045,No.2020BEG03044).
文摘AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was included in the study.Whole-exome sequencing(WES)was initially used to locate copy number variations(CNVs)on 7q31.31-31.32,but failed to detect the precise breakpoint.The long-read sequencing,Oxford Nanopore sequencing Technology(ONT)was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction(QPCR)and Sanger Sequencing.RESULTS:The proband,along with her father and younger brother,were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32,which included the FEVRrelated gene TSPAN12.The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del.The proband exhibited a phase 2A FEVR phenotype,characterized by a falciform retinal fold,macular dragging,and peripheral neovascularization with leaking of fluorescence.These symptoms led to a significant decrease in visual acuity in both eyes.On the other hand,the affected father and younger brother showed a milder phenotype.CONCLUSION:The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype.The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders.
基金Supported by Zhejiang Provincial Health Science and Technology Program of Traditional Chinese Medicine(No.2021ZB284,No.2023ZR053)Science and Technology Bureau of Jiaxing City(No.2021AY30007,No.2021AY30008)Jiaxing Key Laboratory of Diabetic Angiopathy Research(No.2019ZDSYS)。
文摘AIM:To identify and analyze the genotype of the patients with special ocular manifestations of familial vitreous amyloidosis(FVA)in a Chinese Han family.METHODS:Pars plana vitrectomy(PPV)surgery was performed on a 52-year-old Chinese woman presented with vitreous amyloidosis and progressive visual impairment,without evidence of cardiac,renal,gastrointestinal,central nervous system or peripheral nervous system dysfunction.During the surgery,the patient presented with a gray-white dense and thick cotton woollike change in the vitreous body,accompanied by complete retinal detachment.Additionally,hard,free and movable yellow-white deposits were observed in the posterior pole and surrounding retina,the vitreous and subretinal deposits were examined by Congo red staining and immunohistochemical pathological examination,and whole exome sequencing was performed on blood samples from the patient and her cousin.RESULTS:During the operation,it was discovered that there was a complete detachment of the retina and a significant amount of hard,free-floating yellow-white deposits were observed beneath the posterior pole and surrounding retina.This is an exceedingly rare ocular manifestation.Pathological examination of the vitreous and subretinal deposit specimens revealed positive Congo red staining,as well as elevated vascular endothelial growth factor(VEGF)expression in vascular endothelial cells within the sediment specimens upon immunohistochemical examination.The patient and her cousin both exhibited a heterozygous mutation in Glyl03Arg within the transthyretin(TTR)gene,resulting in a substitution of glycine(Gly)at position 103 with arginine(Arg).CONCLUSION:FVA may present with various ocular manifestations,but panretinal detachment is a rare occurrence.In cases where retinal detachment persists for an extended period of time,amyloid deposits may form under the retina through retinal tears,leading to subretinal deposits that can impede retinal reattachment and negatively impact visual prognosis.Elevated levels of VEGF in the eyes of FVA patients may indicate an overexpression state,necessitating careful postoperative follow-up.The heterozygous mutation Gly103Arg may represent a unique pathogenic site in Chinese individuals.
文摘Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease deadly. In Africa, little data exists on this condition and the form familial is the most common with a younger age of onset. Our observations relate to three brothers, born from a consanguineous marriage. The diagnosis of amyotrophic lateral sclerosis was certain placed in all patients according to the criteria of Awaji. The average age of patients was 16.66 years, and the average age of onset of symptoms was 10.33 years old. The female gender was the most represented with a sex ratio of 0.5. Our patients benefited from rilusole, vitamin D and physiotherapy. A only patient presented with dysphagia. However, no cases have been observed at this day.
文摘Objectives: It is to determine the prevalence of familial hypercholesterolemia (FH) among adult Filipino patients with dyslipidemia at Universidad de Santa Isabel Health Services Department in one year. Methods: An observational descriptive prospective study involves Filipino patients, aged 19 years and older, with dyslipidemia. The Dutch Lipid Network (DLN) Criteria was used to diagnose FH. Prevalence data and categorical variables were expressed as percentages, while continuous variables were reported as mean and standard deviations. Results: 529 patients were included in the study. 302 were females, and 227 were males. 180 (34%) scored Unlikely, 100 (19%) scored Probable, 185 (35%) scored Possible, and 64 (12%) were classified under Definite Familial Hypercholesterolemia. Most of the patients diagnosed with definite FH did not have diabetes, cerebrovascular disease (CVD), and coronary artery disease (CAD). The diagnosis was not affected by gender, BMI, smoking, and alcohol consumption. Hypertension was significantly correlated to the diagnosis of FH, as most of them were already hypertensive at diagnosis. It was noted that hypertension, diabetes, CVD, and CAD were seen at an earlier age among patients with definite FH. Conclusion: The prevalence of heterozygous FH at 12% among dyslipidemia patients and 1.3% among the general population was described for the first time in our region. This result should raise the awareness of our healthcare providers that FH, which is a major risk factor for premature CAD and CVD, exists, and early detection and management are important.
文摘In this paper we present a five-generation kindred with familial eosinophilia, associated with valvular heart disease in one of seven members of the second generation, four of sixteen members of the third generation, four of thirty-one members of the fourth generation, and two of twenty members of the fifth generation;the clinical features of the two members of the first generation are unavailable. Of a total of 48 members, 26 had eosinophilia, with counts ranging from 1761 to 6045 cells/mm<sup>3</sup>, with apparent autosomal dominant propagation;this confirms the experience of the authors of previous studies on this condition. Genetic analysis on eight members, which we reported in an earlier paper [1], revealed a pericentric inversion of chromosome 10 in two members. The entity of Familial Eosinophilia has been generally considered benign. However, the clinical presentation of this kindred was unusual in that valvular and endocardial damage, was frequent findings, without apparent involvement of the other organs and tissues. Mitral valve damage leading to both stenosis and regurgitation and requiring mitral valve replacement was noted in the index patient. This unique presentation may suggest that in patients with mitral valve disease, if blood eosinophilia is noted, it could point to a non-rheumatic etiology, thus a possible opportunity for treatment to prevent further damage to the heart. This recommendation may be even more timely, as many effective treatments are now available to treat even high-grade hypereosinophilia.
基金Supported by NIH,No.UG3TR003289 to Soto-Gutierrez A.
文摘Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretion,and/or caused by defects in the secretory machinery of cholangiocytes.Several mutations and pathways that lead to cholestasis have been described.Progressive familial intrahepatic cholestasis(PFIC)is a group of rare diseases caused by autosomal recessive mutations in the genes that encode proteins expressed mainly in the apical membrane of the hepatocytes.PFIC 1,also known as Byler’s disease,is caused by mutations of the ATP8B1 gene,which encodes the familial intrahepatic cholestasis 1 protein.PFIC 2 is characterized by the downregulation or absence of functional bile salt export pump(BSEP)expression via variations in the ABCB11 gene.Mutations of the ABCB4 gene result in lower expression of the multidrug resistance class 3 glycoprotein,leading to the third type of PFIC.Newer variations of this disease have been described.Loss of function of the tight junction protein 2 protein results in PFIC 4,while mutations of the NR1H4 gene,which encodes farnesoid X receptor,an important transcription factor for bile formation,cause PFIC 5.A recently described type of PFIC is associated with a mutation in the MYO5B gene,important for the trafficking of BSEP and hepatocyte membrane polarization.In this review,we provide a brief overview of the molecular mechanisms and clinical features associated with each type of PFIC based on peer reviewed journals published between 1993 and 2020.
文摘In order to compare the clinical characteristics of familial and non-familial bullous lichen planus (BLP), the archival data of 36 BLP patients with positive family history and 21 BLP patients with negative family history diagnosed according to the clinical features and histopathology were collected in our department from 1956 to 2003. The clinical features were analyzed and compared. There were significant differences between familial and non-familial BLP in age of onset, duration of disease and extension of eruption (P<0.01). It was concluded that familial BLP appeared to differ from the non-familial form in its earlier age of onset, longer duration of the disease, more extensive eruption and more tendency to involve nails. Hereditary factors may play a role in the pathogenesis of familial BLP.
文摘BACKGROUND:Three types of progressive familial intrahepatic cholestasis(PFIC)have been identified,but their etiologies include unknown mechanisms. DATA SOURCES:A PubMed search on"progressive familial intrahepatic cholestasis"and"PFIC"was performed on the topic,and the relevant articles were reviewed. RESULTS:The etiologies of the three PFIC types still include unknown mechanisms.Especially in PFIC type 1,enterohepatic circulation of bile acid should be considered.Ursodeoxycholic acid,partial external biliary diversion and liver transplantation have been used for the treatment of PFIC patients according to disease course. CONCLUSIONS:Since the etiologies and disease mechanisms of PFIC are still unclear,detailed studies are urgently required. Strategies for more advanced therapies are also needed.These developments in the future are indispensable,especially for PFIC type 1 patients.
文摘Genotyping is conclusive for the diagnosis of progressive familial intrahepatic cholestasis type 3(PFIC3). Here we report a Chinese patient of PFIC3 with compound mutations in the ABCB4 gene. Liver biopsy was performed on a 17-year-old male patient with intrahepatic cholestasis of unknown etiology. Liver histology findings are indicative of intrahepatic cholestasis with extensive fibrosis. Genotyping revealed c.175C>T(p.L59L) mutation in exon 4, c.504C>T(p.N168N) mutation in exon 6, c.711A>T(p.I237I) mutation in exon 8, c.874A>T(p.K292X) in exon 9 and a novel mutation, c.1804G>T(p.G602W) in exon 15. Based on these findings, the patient was diagnosed with PFIC3. The novel mutation p.G602 W in exon 15 was predicted as probably damaging by Poly Phen-2 with a score of 0.986(sensitivity: 0.54; specificity: 0.94) and was predicted to affect protein function with a SIFT score of 0.01.
文摘BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resulting in a hepatocellular form of cholestasis.While the diagnosis of such disorders had historically been based on pattern recognition of unremitting cholestasis without other identified molecular or anatomic cause,recent scientific advancements have uncovered multiple specific responsible proteins.The variety of identified defects has resulted in an ever-broadening phenotypic spectrum,ranging from traditional benign recurrent jaundice to progressive cholestasis and end-stage liver disease.AIM To review current data on defects in bile acid homeostasis,explore the expanding knowledge base of genetic based diseases in this field,and report disease characteristics and management.METHODS We conducted a systemic review according to PRISMA guidelines.We performed a Medline/PubMed search in February-March 2019 for relevant articles relating to the understanding,diagnosis,and management of bile acid homeostasis with a focus on the family of diseases collectively known as PFIC.English only articles were accessed in full.The manual search included references of retrieved articles.We extracted data on disease characteristics,associations with other diseases,and treatment.Data was summarized and presented in text,figure,and table format.RESULTS Genetic-based liver disease resulting in the inability to properly form and secrete bile constitute an important cause of morbidity and mortality in children and increasingly in adults.A growing number of PFIC have been described based on an expanded understanding of biliary transport mechanism defects and the development of a common phenotype.CONCLUSION We present a summary of current advances made in a number of areas relevant to both the classically described FIC1(ATP8B1),BSEP(ABCB11),and MDR3(ABCB4)transporter deficiencies,as well as more recently described gene mutations--TJP2(TJP2),FXR(NR1H4),MYO5B(MYO5B),and others which expand the etiology and understanding of PFIC-related cholestatic diseases and bile transport.
基金Supported by The National Natural Science Foundation of China,No.30940086
文摘AIM:To study the characteristics of APC(adenomatous polyposis coli)gene germline mutation in Chinese patients with familial adenomatous polyposis(FAP).METHODS:APC gene from 14 FAP families was amplified by polymerase chain reaction(PCR)and underwent direct sequencing to determine the micromutation type.For the samples without micromutation,the large fragment deletion of APC gene was examined by multiplex ligation-dependent probe amplification(MLPA).RESULTS:There were gene micromutations in 9 families with a micromutation detection rate of 64.3%(9/14),including 6 frameshift mutations(66.7%),1 nonsense mutation(11.1%)and 2 splicing mutations(22.2%).Large fragment deletions were detected by MLPA in 2 families.The total mutation detection rate of micromutations and large fragment deletions was 78.6%(11/14).CONCLUSION:The detection rate of APC gene germline mutation can be improved by direct sequencing combined with MLPA large fragment deletion detection.
文摘Familial adenomatous polyposis(FAP) is an autosomal dominant inherited syndrome characterized by multiple adenomatous polyps(predisposing to colorectal cancer development) and numerous extracolonic manifestations. The underlying genetic burden generates variable clinical features that may influence operative management. As a precancerous hereditary condition, the rationale of performing a prophylactic surgery is a mainstay of FAP management. The purpose of the present paper is to bring up many controversial aspects regarding surgical treatment for FAP, and to discuss the results and perspectives of the operative choices and approaches. Preferably, the decision-making process should not be limited to the conventional confrontation of pros and cons of ileorectal anastomosis or restorative proctocolectomy. A wide discussion with the patient may evaluate issues such as age, genotype, family history, sphincter function, the presence or risk of desmoid disease, potential complications of each procedure and chances of postoperative surveillance. Therefore, the definition of the best moment and the choice of appropriate procedure constitute an individual decision that must take into consideration patient's preferences and full information about the complex nature of the disease. All these facts reinforce the idea that FAP patients should be managed by experienced surgeons working in specialized centers to achieve the best immediate and long-term results.
文摘Rhabdomyolysis continues to appear with increasing frequency and represents a medical emergency requiring rapid appropriate treatment. One of the unusual causes of nontraumatic rhabdomyolysis is hypokalemic periodic paralysis without secondary causes. Primary hypokalemic periodic paralysis is a rare genetic disease characterized by episodic attacks of muscle weakness due to decreases in serum potassium. A 30-year-old woman who had 3 episodic attacks of hypokalemic periodic paralysis was admitted in emergency room with sudden onset symmetrical muscle weakness. After several hours, she started to complain myalgia and severe ache in both calves without any changes. Laboratory test showed markedly elevated creatine phosphokinase, lactic dehydrogenase levels with hypokalemia, rhabdomyolysis resulting from hypokalemia was diagnosed. Here, we report an unusual case of rhabdomyolysis caused by severe hypokalemia, which was suggested a result of familial hypokalemic periodic paralysis.
文摘Patients with familial adenomatous polyposis(FAP),an autosomal dominant hereditary colorectal cancer syndrome,have a lifetime risk of developing cancer of nearly 100%.Recent studies have pointed out that the gut microbiota could play a crucial role in the development of colorectal adenomas and the consequent progression to colorectal cancer.Some gut bacteria,such as Fusobacterium nucleatum,Escherichia coli,Clostridium difficile,Peptostreptococcus,and enterotoxigenic Bacteroides fragilis,could be implicated in colorectal carcinogenesis through different mechanisms,including the maintenance of a chronic inflammatory state,production of bioactive tumorigenic metabolites,and DNA damage.Studies using the adenomatous polyposis coliMin/+mouse model,which resembles FAP in most respects,have shown that specific changes in the intestinal microbial community could influence a multistep progression,the intestinal“adenoma-carcinoma sequence”,which involves mucosal barrier injury,low-grade inflammation,activation of the Wnt pathway.Therefore,modulation of gut microbiota might represent a novel therapeutic target for patients with FAP.Administration of probiotics,prebiotics,antibiotics,and nonsteroidal anti-inflammatory drugs could potentially prevent the progression of the adenoma-carcinoma sequence in FAP.The aim of this review was to summarize the best available knowledge on the role of gut microbiota in colorectal carcinogenesis in patients with FAP.
文摘Restorative proctocolectomy is the most common surgical option for patients with familial adenomatous polyposis(FAP). However,adenomas may develop in the ileal pouch mucosa over time,and even carcinoma in the pouch has been reported. We therefore reviewed the prevalence,nature,and treatment of adenomas and carcinoma that develop after proctocolectomy in the ileal pouch mucosa in patients with FAP. In 25 reports that were reviewed,the incidence of adenomas in the ileal pouch varied from 6.7% to 73.9%. Several potential factors that favor the development of pouch polyposis have been investigated,but many remain controversial. Nevertheless,it seems certain that the age of the pouch is important. The risk appears to be 7%to 16% after 5 years,35% to 42% after 10 years,and75% after 15 years. On the other hand,only 21 cases of ileal pouch carcinoma have been recorded in the literature to date. The diagnosis of pouch carcinoma was made between 3 to 20 years(median,10 years) after pouch construction. Although the risk of malignant transformation in ileal pouches is probably low,it is not negligible,and the long-term risk cannot presently be well quantified. Regular endoscopic surveillance,especially using chromoendoscopy,is recommended.
基金Supported by Sanming Project of Medicine in Shenzhen of China,No.SZSM201612074
文摘BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)encompasses a group of autosomal recessive disorders with high morbidity and mortality.Variants in the gene encoding tight junction protein-2(TJP2)have been linked to PFIC type 4(PFIC4),which predominantly presents in childhood.However,there are only limited data from adults with TJP2-related PFIC4.We report a family with an autosomal recessive disorder with a novel variant in the TJP2 gene in adults with very variable expression of PFIC4.CASE SUMMARY The index patient presented at 19 years old with liver cirrhosis and variceal bleeding and was treated with endoscopic banding and beta-blockers.In 2018,he developed primary liver cancer that was treated with radiofrequency ablation followed by liver transplantation in 2019.Genetic testing revealed a novel homozygous TJP2 variant causing PFIC4(TJP2([NM_004817.3]:c.[3334C>T];[3334C>T])).The consanguineous family consists of the father and mother(both heterozygous)and their 12 children,of which five carry the variant in a homozygous state;however,these five siblings have highly variable expression of PFIC4.Two homozygous brothers had cirrhosis and portal hypertension at diagnosis at the ages of 19 and 36.Two other homozygous brothers,age 23 and 19,and the homozygous sister,age 21,have elevated liver enzymes but presently no cirrhosis,which may suggest an age-dependent penetrance.In addition,five sisters had severe and mild intrahepatic cholestasis of pregnancy and carry the TJP2 variant in a homozygous and heterozygous state,respectively.CONCLUSION This novel TJP2 variant is associated with PFIC4 causing severe liver disease with cirrhosis and primary liver cancer in adolescents/adults.
文摘Progressive familial intrahepatic cholestasis type 3 is caused by a mutation in the ATP-binding cassette, subfamily B, member 4 (ABCB4) gene encoding multidrug resistance protein 3. A 32-year-old woman with a history of acute hepatitis at age 9 years was found to have jaundice during pregnancy in 2008, and was diagnosed as having intrahepatic cholestasis of pregnancy. In 2009, she underwent cholecystectomy for gallstones and chronic cholecystitis. However, itching and jaundice did not resolve postoperatively. She was admitted to our hospital with fatigue, jaundice, and a recently elevated γ-glutamyl transpeptidase level. Liver biopsy led to the diagnosis of biliary cirrhosis with ductopenia. Genetic testing revealed a pathogenic heterozygous mutation, ex13 c.1531G > A (p.A511 T), in the ABCB4 gene. Her father did not carry the mutation, but her mother's brother carried the heterozygous mutation. We made a definitivediagnosis of familial intrahepatic cholestasis type 3. He symptoms and liver function improved after 3 mo o treatment with ursodeoxycholic acid.
