期刊文献+
共找到27篇文章
< 1 2 >
每页显示 20 50 100
The pathogenic mechanism of syndactyly type V identified in aHoxd13Q50R knock-in mice
1
作者 Han Wang Xiumin Chen +6 位作者 Xiaolu Meng Yixuan Cao Shirui Han Keqiang Liu Ximeng Zhao Xiuli Zhao Xue Zhang 《Bone Research》 SCIE CAS CSCD 2024年第2期349-360,共12页
Syndactyly type V (SDTY5) is an autosomal dominant extremity malformation characterized by fusion of the fourth and fifthmetacarpals. In the previous publication, we first identified a heterozygous missense mutation Q... Syndactyly type V (SDTY5) is an autosomal dominant extremity malformation characterized by fusion of the fourth and fifthmetacarpals. In the previous publication, we first identified a heterozygous missense mutation Q50R in homeobox domain (HD) ofHOXD13 in a large Chinese family with SDTY5. In order to substantiate the pathogenicity of the variant and elucidate the underlyingpathogenic mechanism causing limb malformation, transcription-activator-like effector nucleases (TALEN) was employed togenerate a Hoxd13Q50R mutant mouse. The mutant mice exhibited obvious limb malformations including slight brachydactyly andpartial syndactyly between digits 2-4 in the heterozygotes, and severe syndactyly, brachydactyly and polydactyly in homozygotes.Focusing on BMP2 and SHH/GREM1/AER-FGF epithelial mesenchymal (e-m) feedback, a crucial signal pathway for limbdevelopment, we found the ectopically expressed Shh, Grem1 and Fgf8 and down-regulated Bmp2 in the embryonic limb bud atE10.5 to E12.5. A transcriptome sequencing analysis was conducted on limb buds (LBs) at E11.5, revealing 31 genes that exhibitednotable disparities in mRNA level between the Hoxd13Q50R homozygotes and the wild-type. These genes are known to be involvedin various processes such as limb development, cell proliferation, migration, and apoptosis. Our findings indicate that the ectopicexpression of Shh and Fgf8, in conjunction with the down-regulation of Bmp2, results in a failure of patterning along both theanterior-posterior and proximal-distal axes, as well as a decrease in interdigital programmed cell death (PCD). This cascadeultimately leads to the development of syndactyly and brachydactyly in heterozygous mice, and severe limb malformations inhomozygous mice. These findings suggest that abnormal expression of SHH, FGF8, and BMP2 induced by HOXD13Q50R may beresponsible for the manifestation of human SDTY5. 展开更多
关键词 BMP2 MECHANISM finding
下载PDF
Implementing comprehensive genetic carrier screening in China―Harnessing the power of genomic medicine for the effective prevention/management of birth defects and rare genetic diseases in China 被引量:6
2
作者 Yiping Shen Xiaoxia Qiu +6 位作者 Baohen Gui Sheng He Hefeng Huang Jingjie Xue Xiangming Xu Xue Zhang Lin He 《Pediatric Investigation》 2018年第1期30-36,共7页
Carrier screening had been demonstrated as a powerful practice in preventing selected severe genetic disorders. This practice is expanding its scope and impact in the era of next-generation sequencing. Empirical and t... Carrier screening had been demonstrated as a powerful practice in preventing selected severe genetic disorders. This practice is expanding its scope and impact in the era of next-generation sequencing. Empirical and theoretical data support the utility of expanded carrier screening. The authors propose a comprehensive carrier screening program as a main component of the first-tier measure in preventing severe genetic disorders and birth defects in China. We discussed the key principles and important aspects to ensure the success of such a program. The authors believe this program will play a pivotal role in our endeavor for a healthier nation. 展开更多
关键词 Carrier screening Next generation SEQUENCING BIRTH defect GENETIC disease
原文传递
T2T-YAO Reference Genome of Han Chinese--New Step in Advancing Precision Medicine in China
3
作者 Xue Zhang 《Genomics, Proteomics & Bioinformatics》 SCIE CAS CSCD 2023年第6期1083-1084,共2页
One of the many aims of precision medicine is to tailor disease prevention,including diagnostics and treatment,to everyone’s genetic makeup.Its foundation is built upon a set of linear chromosome sequences with outst... One of the many aims of precision medicine is to tailor disease prevention,including diagnostics and treatment,to everyone’s genetic makeup.Its foundation is built upon a set of linear chromosome sequences with outstanding accuracy,and it is such accuracy that assures the maximal anchorage of genetic and physical markers for disease mapping and molecular studies.In addition to the quality of a reference genome,its relevance to a real population is crucial;T2T-YAO represents one of the aboriginal Han Chinese populations born along the Yellow River basin[1]. 展开更多
关键词 MAXIMAL ADDITION FOUNDATION
原文传递
Restrictive Cardiomyopathy Resulting from a Troponin Ⅰ Type 3 Mutation in a Chinese Family 被引量:3
4
作者 Yan-ping Ruan Chao-xia Lu +6 位作者 Xiao-yi Zhao Rui-juan Liang Hui Lian Michael Routledge Wei Wu Xue Zhang Zhong-jie Fan 《Chinese Medical Sciences Journal》 CAS CSCD 2016年第1期1-7,共7页
Objective To identify the pathogenic variant responsible for restrictive cardiomyopathy (RCM) in aChinese family.Methods Next generation sequencing was used for detecting the mutation and results verified bysequenci... Objective To identify the pathogenic variant responsible for restrictive cardiomyopathy (RCM) in aChinese family.Methods Next generation sequencing was used for detecting the mutation and results verified bysequencing. We used restriction enzyme digestion to test the mutation in the family members and 200 unrelatednormal subjects without any cardiac inherited diseases when the mutation was identified.Results Five individuals died from cardiac diseases, two of whom suffered from sudden cardiacdeath. Two individuals have suffered from chronic cardiac disorders. Mutation analysis revealed a novelmissense mutation in exon 7 of troponin I type 3 (TNNI3), resulting in substitution of serine (S) withproline (P) at amino acid position 150, which cosegregated with the disease in the family, which is predictedto be probably damaging using PolyPhen-2. The mutation was not detected in the 200 unrelated subjectswe tested.Conclusion Using next generation sequencing, which has very recently been shown to be successfulin identifying novel causative mutations of rare Mendelian disorders, we found a novel mutation of TNNI3 in aChinese family with RCM. 展开更多
关键词 restrictive cardiomyopathy autosomal dominant troponin I
下载PDF
Towards key scientific questions in the diagnosis and treatment of rare diseases: Summary from the 297th Meeting of the Shuangqing Forum 被引量:1
5
作者 Cai-Yun Zhu Wei Hong +2 位作者 Lei Wang Li-Jun Ding Xue Zhang 《Zoological Research》 SCIE CAS CSCD 2022年第2期234-236,共3页
In China,rare diseases are defined as having a birth incidence of less than 1/10000,or a prevalence of less than 1/10000 or less than 140000 patients.Over 7000 rare diseases affect more than 20 million people in China... In China,rare diseases are defined as having a birth incidence of less than 1/10000,or a prevalence of less than 1/10000 or less than 140000 patients.Over 7000 rare diseases affect more than 20 million people in China.Many conditions are misdiagnosed or undiagnosed and most have no treatment,resulting in a huge burden on patients,their families,and the national economy.At the 297th Shuangqing Forum of the National Natural Science Foundation of China,we highlighted the challenges and potential solutions to achieve precision medicine for undiagnosed and rare diseases. 展开更多
关键词 diagnosis treatment FORUM
下载PDF
Genetic Testing of the mucin I gene-Variable Number Tandem Repeat Single Cytosine Insertion Mutation in a Chinese Family with Medullary Cystic Kidney Disease
6
作者 Nuo Si Ke Zheng +3 位作者 Jie Ma Xiao-Lu Meng Xue-Mei Li Xue Zhang 《Chinese Medical Journal》 SCIE CAS CSCD 2017年第20期2459-2464,共6页
Background: Medullary cystic kidney disease (MCKD) is clinically indistinguishable from several other autosomal-dominant renal diseases: thus, molecular genetic testing is needed to establish a definitive diagnosi... Background: Medullary cystic kidney disease (MCKD) is clinically indistinguishable from several other autosomal-dominant renal diseases: thus, molecular genetic testing is needed to establish a definitive diagnosis. A specific type of single cytosine insertion in the variable number tandem repeat (VNTR) of the mucin 1 (MUC1) gene is the only known cause of MCKD1; however, genetic analysis of this mutation is difficult and not yet offered routinely. To identify the causative mutation/s and establish a definitive diagnosis in a Chinese family with chronic kidney disease, clinical assessments and genetic analysis were performed, including using a modified genotyping method to identify the MUC1-VNTR single cytosine insertion. Methods: Clinical data from three patients in a Chinese family with chronic kidney disease were collected and evaluated. Linkage analysis was used to map the causative locus. Mutation analysis of uromodulin (UMOD) gene was performed using polymerase chain reaction (PCR) and direct sequencing. For MUC1 genotyping, the mutant repeat units were enriched by Mwol restriction, and then were amplified and introduced into pMD-18T vectors. The 192 clones per transformant were picked up and tested by colony PCR and second round of Mwol digestion. Finally, Sanger sequencing was used to confirm the MUC1 mutation. Results: Clinical findings and laboratory results were consistent with a tubulointerstitial lesion. Linkage analysis indicated that the family was compatible with the MCKDI locus. No mutations were found in UMOD gene. Using the modified MUC1 genotyping method, we detected the MUC1-VNTR single cytosine insertion events in three patients of the family; and mutation-containing clones were 12/192, 14/192, and 5/96, respectively, in the three patients. Conclusions: Clinical and genetic findings could support the MCKDI diagnosis. The modified strategy has been demonstrated to be a practical way to detect MUCI mutation. 展开更多
关键词 Autosomal Dominant Tubulointerstitial Kidney Diseases GENOTYPING Medullary Cystic Kidney Disease MUC1 Gene Variable Number Tandem Repeat
原文传递
A novel phenotype with splicing mutation identified in a Chinese family with desminopathy
7
作者 Peng Fan Xueqi Dong +12 位作者 Di Zhu Kunqi Yang Keqiang Liu Di Zhang Ying Zhang Xu Meng Huiqiong Tan Litian Yu Kefei Dou Yaxin Liu Chaoxia Lu Xue Zhang Xianliang Zhou 《中国循环杂志》 CSCD 北大核心 2018年第S01期123-124,共2页
Background and Objective Desminopathy is a largely heterogeneous group of conditions involving inherited or sporadic myofibrillar myopathy.In terms of its mode of inheritance,the autosomal dominant form is predominant... Background and Objective Desminopathy is a largely heterogeneous group of conditions involving inherited or sporadic myofibrillar myopathy.In terms of its mode of inheritance,the autosomal dominant form is predominant.Desmin gene(DES)mutations play a critical role among the pathogenic inherited factors associated with desminopathy.Desminopathy involves various phenotypes,mainly including different cardiomyopathies,skeletal myopathy and arrhythmia.The purposes of this study are characterization of a novel phenotype and identification of a DES splicing mutation in a Chinese family with desminnopathy. 展开更多
关键词 CHINESE FAMILY with DESMINOPATHY NOVEL PHENOTYPE DES
下载PDF
Building a modern six-dimensional biobank fosters the future of precision medicine
8
作者 Tian-Yu Lian Yi Yan +3 位作者 Dong Ding Yue-Jiao Ma Xue Zhang Zhi-Cheng Jing 《Science Bulletin》 SCIE EI CAS CSCD 2022年第24期2490-2493,共4页
In 2001, Dr. Zhi-Cheng Jing encountered a pulmonary arterial hypertension (PAH) patient from a large pedigree. Dr. Jing collected the clinical information and blood samples from this pedigree and was the first to repo... In 2001, Dr. Zhi-Cheng Jing encountered a pulmonary arterial hypertension (PAH) patient from a large pedigree. Dr. Jing collected the clinical information and blood samples from this pedigree and was the first to report the pedigree of familial PAH in China [1]. In2004, this pedigree was confirmed to carry a mutation in BMPR2(Arg491Trp), which was the first evidence of pathogenicity of BMPR2 mutation in the Chinese population [2]. 展开更多
关键词 罕见病 新药研发 生物样本 ARTERIAL HYPERTENSION
原文传递
Phenotypic and genetic characterization of novel variant in the NF1 gene underlying neurofibromatosis type 1 in five Chinese families
9
作者 Xiaerbati Habulieti Liwei Sun +5 位作者 Jiawei Liu Kexin Guo Xueting Yang Rongrong Wang Donglai Ma Xue Zhang 《Science China(Life Sciences)》 SCIE CAS CSCD 2021年第12期2206-2209,共4页
Dear Editor,Neurofibromatosis type 1(NF1;von Recklinghausen neurofibromatosis;OMIM 162200)is a neurocutaneous genetic disorder that affects approximately one in 2,500 people worldwide(Huson et al.,1989).NF1 is charact... Dear Editor,Neurofibromatosis type 1(NF1;von Recklinghausen neurofibromatosis;OMIM 162200)is a neurocutaneous genetic disorder that affects approximately one in 2,500 people worldwide(Huson et al.,1989).NF1 is characterized by wide clinical variability,including multiple café-au-lait macules(CALMs),fibromatous tumors,axillary or inguinal freckling,Lisch nodules(iris hamartomas),skeletal anomalies,and cognitive impairments(Monroe et al.,2017). 展开更多
关键词 NF1 IMPAIRMENT
原文传递
Dysregulated N6-methyladenosine modification in peripheral immune cells contributes to the pathogenesis of amyotrophic lateral sclerosis
10
作者 Di He Xunzhe Yang +5 位作者 Liyang Liu Dongchao Shen Qing Liu Mingsheng Liu Xue Zhang Liying Cui 《Frontiers of Medicine》 SCIE CSCD 2024年第2期285-302,共18页
Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain origins.Emerging evidence implicates N6-methyladenosine(m6A)modification in ALS pathogenesis.Methylated RNA immunoprecipitatio... Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain origins.Emerging evidence implicates N6-methyladenosine(m6A)modification in ALS pathogenesis.Methylated RNA immunoprecipitation sequencing(MeRIP-seq)and liquid chromatography–mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis,respectively,in patients with ALS(n=16)and controls(n=6).The single-cell transcriptomic dataset(GSE174332)of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication changes.Analysis of peripheral immune cells revealed extensive RNA hypermethylation,highlighting candidate genes with differential m6A modification and expression,including C-X3-C motif chemokine receptor 1(CX3CR1).In RAW264.7 macrophages,disrupted CX3CR1 signaling affected chemotaxis,potentially influencing immune cell migration in ALS.Serum proteome analysis demonstrated the role of dysregulated immune cell migration in ALS.Cell type-specific expression variations of these genes in the central nervous system(CNS),particularly microglia,were observed.Intercellular communication between neurons and glial cells was selectively altered in ALS CNS.This integrated approach underscores m6A dysregulation in immune cells as a potential ALS contributor. 展开更多
关键词 amyotrophic lateral sclerosis N^(6)-methyladenosine epi-transcriptome PROTEOME single cell RNA sequencing analysis CX3CR1
原文传递
Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function variants in TMEM141,DDHD2,and LHFPL5
11
作者 Liwei Sun Xueting Yang +7 位作者 Amjad Khan Xue Yu Han Zhang Shirui Han Xiaerbati Habulieti Yang Sun Rongrong Wang Xue Zhang 《Frontiers of Medicine》 SCIE CSCD 2024年第1期81-97,共17页
Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine.Panoramic variation analysis is imperative to analyze the disease phenotypes resul... Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine.Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation.Here,a Pakistani family with parental consanguinity was presented,characterized with severe intellectual disability(ID),spastic paraplegia,and deafness.Homozygosity mapping,integrated single nucleotide polymorphism(SNP)array,whole-exome sequencing,and whole-genome sequencing were performed,and homozygous variants in TMEM141(c.270G>A,p.Trp90^(*)),DDHD2(c.411+767_c.1249-327del),and LHFPL5(c.250delC,p.Leu84^(*))were identified.A Tmem141^(p.Trp90^(*)/p.Trp90^(*))mouse model was generated.Behavioral studies showed impairments in learning ability and motor coordination.Brain slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje cells.Transmission electron microscopy showed abnormal mitochondrial morphology.Furthermore,studies on a human in vitro neuronal model(SH-SY5Y cells)with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function,possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse model.Conclusively,panoramic variation analysis revealed that multilocus genomic variations of TMEM141,DDHD2,and LHFPL5 together caused variable phenotypes in patient.Notably,the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID. 展开更多
关键词 neurodevelopmental disorder autosomal recessive intellectual DISABILITY CONSANGUINITY spastic paraplegia hearing loss TMEM141
原文传递
A novel homozygous intronic variant affecting splicing in the RYR1 gene contributes to fetal hydrops
12
作者 Wei Hou Guifang Huang +7 位作者 Hongyu Wei Wenwei Li Houfeng Huang Yuling Qiu Hengying Zhu Huifeng Han Ping Chen Xue Zhang 《Genes & Diseases》 SCIE CSCD 2024年第6期107-110,共4页
Fetal hydrops is a rare but serious fetal developmental abnormality characterized by the abnormal accumulation of large amounts of fluid in the fetus resulting in generalized edema,and clinically manifested by abnorma... Fetal hydrops is a rare but serious fetal developmental abnormality characterized by the abnormal accumulation of large amounts of fluid in the fetus resulting in generalized edema,and clinically manifested by abnormal functioning of multiple organs and systems.1 The ryanodine receptor 1(RYR1)gene encodes the ryanodine receptor found in skeletal muscle and is expressed predominantly in cardiac and skeletal muscle. 展开更多
关键词 FETAL ORGANS FETUS
原文传递
The spectrum of rare monogenic diseases in patients with premature coronary artery disease
13
作者 Yaqun Teng Tian Du +13 位作者 Siqin Feng Ran Tian Yaping Liu Jian Guo Lei Wang Zhiyu Zhang Xiaodong Luan Shan He Shengsheng Zhuang Yifei Wang Shuyuan Zhang Shi Chen Zhenyu Liu Shuyang Zhang 《Chinese Medical Journal》 SCIE CAS CSCD 2024年第10期1246-1248,共3页
To the Editor:The global burden of premature coronary artery disease(CAD)is increasing among the young population.Premature CAD generally refers to the occurrence of obstructive coronary atherothrombotic lesions in me... To the Editor:The global burden of premature coronary artery disease(CAD)is increasing among the young population.Premature CAD generally refers to the occurrence of obstructive coronary atherothrombotic lesions in men and women aged<55 years and<65 years,respectively,and particularly in those aged<45 years.[1]The incidence of CAD in the younger population has remained stable or has increased,despite the declining incidence in older adults.Patients with premature CAD have a poor long-term prognosis,experiencing a high rate of recurrent ischemic events,rapid progression to multivessel disease,and frequent premature death.[1]Thus,it is crucial to identify the underlying causes of premature CAD that are distinct from those of age-related CAD and improve patient outcomes through precise diagnosis and treatment. 展开更多
关键词 PREMATURE YOUNGER PRECISE
原文传递
Lack of CFAP54 causes primary ciliary dyskinesia in a mouse model and human patients
14
作者 Xinyue Zhao Haijun Ge +8 位作者 Wenshuai Xu Chongsheng Cheng Wangji Zhou Yan Xu Junping Fan Yaping Liu Xinlun Tian Kai-Feng Xu Xue Zhang 《Frontiers of Medicine》 SCIE CSCD 2023年第6期1236-1249,共14页
Primary ciliary dyskinesia(PCD)is a highly heterogeneous recessive inherited disorder.FAP54,the homolog of CFAP54 in Chlamydomonas reinhardtii,was previously demonstrated as the C1d projection of the central microtubu... Primary ciliary dyskinesia(PCD)is a highly heterogeneous recessive inherited disorder.FAP54,the homolog of CFAP54 in Chlamydomonas reinhardtii,was previously demonstrated as the C1d projection of the central microtubule apparatus of flagella.A Cfap54 knockout mouse model was then reported to have PCD-relevant phenotypes.Through whole-exome sequencing,compound heterozygous variants c.2649_2657delinC(p.E883Dfs*47)and c.7312_7313insCGCAGGCTGAATTCTTGG(p.T2438delinsTQAEFLA)in a new suspected PCD-relevant gene,CFAP54,were identified in an individual with PCD.Two missense variants,c.4112A>C(p.E1371A)and c.6559C>T(p.P2187S),in CFAP54 were detected in another unrelated patient.In this study,a minigene assay was conducted on the frameshift mutation showing a reduction in mRNA expression.In addition,a CFAP54 in-frame variant knock-in mouse model was established,which recapitulated the typical symptoms of PCD,including hydrocephalus,infertility,and mucus accumulation in nasal sinuses.Correspondingly,two missense variants were deleterious,with a dramatic reduction in mRNA abundance from bronchial tissue and sperm.The identification of PCD-causing variants of CFAP54 in two unrelated patients with PCD for the first time provides strong supportive evidence that CFAP54 is a new PCD-causing gene.This study further helps expand the disease-associated gene spectrum and improve genetic testing for PCD diagnosis in the future. 展开更多
关键词 primary ciliary dyskinesia CFAP54 CILIA
原文传递
Application of next-generation sequencing to screen for pathogenic mutations in 123 unrelated Chinese patients with Marfan syndrome or a related disease 被引量:4
15
作者 Jiacheng Li Chaoxia Lu +6 位作者 Wei Wu Yaping Liu Rongrong Wang Nuo Si Xiaolu Meng Shuyang Zhang Xue Zhang 《Science China(Life Sciences)》 SCIE CAS CSCD 2019年第12期1630-1637,共8页
Marfan syndrome(MFS) is a systemic connective tissue disease principally affecting the ocular, skeletal and cardiovascular systems. This autosomal dominant disorder carries a prevalence of 1:3,000 to 1:5,000. This stu... Marfan syndrome(MFS) is a systemic connective tissue disease principally affecting the ocular, skeletal and cardiovascular systems. This autosomal dominant disorder carries a prevalence of 1:3,000 to 1:5,000. This study aims to define the mutational spectrum of MFS related genes in Chinese patients and to establish genotype-phenotype correlations in MFS. Panel-based targeted next-generation sequencing was used to analyze the FBN1, TGFBR1 and TGFBR2 genes in 123 unrelated Chinese individuals with MFS or a related disease. Genotype-phenotype correlation analyses were performed in mutation-positive patients. The results showed that 97 cases/families(78.9%;97/123) harbor at least one(likely) pathogenic mutation, most of which were in FBN1;four patients had TGFBR1/2 mutations;and one patient harbored a SMAD3 mutation. Three patients had two FBN1 mutations, and all patients showed classical MFS phenotypes. Patients with a dominant negative-FBN1 mutation had a higher prevalence of ectopia lentis(EL). Patients carrying a haploinsufficiency-FBN1 mutation tended to have aortic dissection without EL. This study extends the spectrum of genetic backgrounds of MFS and enriches our knowledge of genotype-phenotype correlations. 展开更多
关键词 Marfan syndrome FBN1 mutation next-generation sequencing genotype-phenotype correlations
原文传递
Keratin 5-Cre-driven deletion of Ncstn in an acne inversa-like mouse model leads to a markedly increased IL-36a and Sprr2 expression 被引量:3
16
作者 Jun Yang Lianqing Wang +6 位作者 Yingzhi Huang Keqiang Liu Chaoxia Lu Nuo Si Rongrong Wang Yaping Liu Xue Zhang 《Frontiers of Medicine》 SCIE CAS CSCD 2020年第3期305-317,共13页
Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in y-secretase component genes.We and other researchers showed that nicastrin (NCSTN) ... Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in y-secretase component genes.We and other researchers showed that nicastrin (NCSTN) is the most frequently mutated gene in familial AI.In this study,we generated a keratin 5-Cre-driven epidermis-specific Ncstn conditional knockout mutant in mice.We determined that this mutant recapitulated the major phenotypes of AI,including hyperkeratosis of hair follicles and inflammation.In Ncstnflox/flox;K5-Cre mice,the IL-36a expression level markedly increased starting from postnatal day 0 (P0),and this increase occurred much earlier than those of TNF-α,IL-23A,IL-1 3,and TLR4.RNA-Seq analysis indicated that Sprr2d,a member of the small proline-rich protein 2 family,in the skin tissues of the Ncstnflox/flox,;K5-Cre mice was also upregulated on P0.Quantitative reverse-transcription polymerase chain reaction showed that other Sprr2 genes had a similar expression pattern.Our findings suggested that IL-36a might be a key inflammatory cytokine in the pathophysiology of AI and implicate malfunction of the skin barrier in the pathogenesis of AI. 展开更多
关键词 acne inversa mouse model interleukin 1 family member 6 small proline rich protein 2D key inflammatory cytokine
原文传递
Novel Mutations in Extracellular Matrix Protein 1 Gene in a Chinese Patient with Lipoid Proteinosis 被引量:4
17
作者 Xiao Bai Jia-Wei Liu Dong-Lai Ma 《Chinese Medical Journal》 SCIE CAS CSCD 2016年第22期2765-2766,共2页
Lipoid proteinosis (LP,OMIM 247100),also known as Urbach-Wiethe disease or lipoidosis cutis et mucosae,was first described by Urbach and Wiethe in 1929.It is a rare autosomal recessive genodermatosis characterized b... Lipoid proteinosis (LP,OMIM 247100),also known as Urbach-Wiethe disease or lipoidosis cutis et mucosae,was first described by Urbach and Wiethe in 1929.It is a rare autosomal recessive genodermatosis characterized by hoarseness from early infancy,distinctive skin and neurological manifestations,and cutaneous lesions.It affects mucosal membranes of the upper respiratory tract,upper digestive tract,central nervous system,lymph nodes,and striated muscles.Hamada identified the genetic defect to be a loss-of-function mutation or reduced expression of the gene encoding extracellular matrix protein 1 (ECM1) on chromosome lq21 in 2002.So far,approximately,300 cases have been reported.This article reported a case with clinical and molecular findings compatible with LP. 展开更多
关键词 Extracellular Matrix Protein 1 Lipoid Protemosis MUTATION
原文传递
A novel phenotype with splicing mutation identified in a Chinese family with desminopathy 被引量:3
18
作者 Peng Fan Chao-Xia Lu +12 位作者 Xue-Qi Dong Di Zhu Kun-Qi Yang Ke-Qiang Liu Di Zhang Ying Zhang Xu Meng Hui-Qiong Tan Li-Tian YU Ke-Fei DOU Ya-Xin Liu Xue Zhang Xian-Liang Zhou 《Chinese Medical Journal》 SCIE CAS CSCD 2019年第2期127-134,共8页
Background:Desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) mutations.Desminopathy involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy... Background:Desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) mutations.Desminopathy involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy, and arrhythmia.Combined with genotype, it helps us precisely diagnose and treat for desminopathy.Methods:Sanger sequencing was used to characterize DES variation, and then a minigene assay was used to verify the effect of splice-site mutation on pre-mRNA splicing.Phenotypes were analyzed based on clinical characteristics associated with desminopathy.Results:A splicing mutation (c.735+1G>T) in DES was detected in the proband.A minigene assay revealed skipping of the whole exon 3 and transcription of abnormal pre-mRNA lacking 32 codons.Another affected family member who carried the identical mutation, was identified with a novel phenotype of desminopathy, non-compaction of ventricular myocardium.There were 2 different phenotypes varied in cardiomyopathy and skeletal myopathy among the 2 patients, but no significant correlation between genotype and phenotype was identified.Conclusions:We reported a novel phenotype with a splicing mutation in DES, enlarging the spectrum of phenotype in desminopathy.Molecular studies of desminopathy should promote our understanding of its pathogenesis and provide a precise molecular diagnosis of this disorder, facilitating clinical prevention and treatment at an early stage. 展开更多
关键词 DESMINOPATHY CARDIOMYOPATHY DESMIN gene SPLICING MUTATION
原文传递
Agraphia in Amyotrophic Lateral Sclerosis with Frontotemporal Lobe Degeneration 被引量:3
19
作者 Bo Cui Li-Ying Cui +5 位作者 Jing Gao Cai-Yan Liu Qing Liu Ming-Sheng Liu Dong-Chao Shen Fang Liu 《Chinese Medical Journal》 SCIE CAS CSCD 2016年第5期612-614,共3页
Frontotemporal lobe degeneration (FTLD) refers to a neurodegenerative dementia syndrome, which could be clinically classified into behavioral and language variant. Amyotrophic lateral sclerosis (ALS) is a progress... Frontotemporal lobe degeneration (FTLD) refers to a neurodegenerative dementia syndrome, which could be clinically classified into behavioral and language variant. Amyotrophic lateral sclerosis (ALS) is a progressive neurological disorder involving both upper motor neuron (UMN) and lower motor neuron (LMN), eventually leading to muscle atrophy and weakness, bulbar palsy, and respiratory failure. 展开更多
关键词 AGRAPHIA Amyotrophic Lateral Sclerosis Frontotemporal Lobe Degeneration
原文传递
Diagnosis with Multiple Epiphyseal Dysplasia Using Whole-exome Sequencing in a Chinese Family 被引量:2
20
作者 Hong-Yan Liu Ji-Fang Xiao +9 位作者 Jia Huang Yue Wang Dong Wu Tao Li Hong-Dan Wang Liang-Jie Guo Qian-Nan Guo Hai Xiao Xue Lyu Zheng-Hong Yu 《Chinese Medical Journal》 SCIE CAS CSCD 2017年第1期104-107,共4页
Multiple epiphyseal dysplasia (MED; EDMI, OMIM 132400; EDM2, OMIM 600204; EDM3, OMIM 600969; EDM4, OMIM 226900; EDM5~ OMIM 607078; EDM6, OMIM 614135) is an autosomal dominant inherited disease of the skeletal system... Multiple epiphyseal dysplasia (MED; EDMI, OMIM 132400; EDM2, OMIM 600204; EDM3, OMIM 600969; EDM4, OMIM 226900; EDM5~ OMIM 607078; EDM6, OMIM 614135) is an autosomal dominant inherited disease of the skeletal system, characterized by mild short stature and early-onset degenerative joint disease, caused by heterogeneous genotypes involving more than six genes (COMP, COL9A 1, COL9A2, COL9A3, MATN3, DTDST).However, in approximately 10-20% of all samples analyzed, a mutation cannot be identified in any of the six genes mentioned above, suggesting that the presence of other unidentified causative genes is also involved in the pathogenesis of MED. 展开更多
关键词 Avascular Necrosis of the Femoral Head Cartilage Oligomeric Matrix Protein Collagen Type II Alpha 1 DIFFERENTIALDIAGNOSIS Whole-exome Sequencing
原文传递
上一页 1 2 下一页 到第
使用帮助 返回顶部