Introduction: Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. Patients and Methods: In the present study, we pres...Introduction: Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. Patients and Methods: In the present study, we present a case of FOP with marked progressive ossification of extraskeletal tissues. We investigated whether soluble factors in serum would affect the osteoblast phenotype by examining the effects of serum from this patient and control subjects on mouse osteoblastic MC3T3-E1 cells. Results: The clinical findings of this patient were compatible with FOP, and direct sequence analysis of genomic DNA demonstrated the presence of a heterozygous 617G> A (R206H) mutation of activin type 1 receptor (ACVR1). Serum from the FOP patient enhanced the level of alkaline phosphatase (ALP) in Western blotting, compared with serum from the control, in MC3T3-E1 cells. Moreover, serum from the FOP patient enhanced the levels of ALP, osteocalcin and bone morphogenetic protein-2 mRNA in these cells. Conclusion: We presented a case of FOP with progressive ossification in extra-skeletal tissues with ACVR1 mutation. The present data suggest that the serum from this patient includes some soluble factors, which might enhance the osteoblast differentiation and BMP-2 expression in mouse osteoblastic cells.展开更多
Background Fibrodysplasia ossificans progressiva(FOP)is a rare and disabling heritable connective tissue disease that is difficult to treat.This study seeks to explore the clinical characteristics,clinical manifestati...Background Fibrodysplasia ossificans progressiva(FOP)is a rare and disabling heritable connective tissue disease that is difficult to treat.This study seeks to explore the clinical characteristics,clinical manifestations,treatment and prognosis of FOP to provide a clinical basis for its early diagnosis and treatment.Methods Twenty-six children with FOP were retrospectively analyzed in terms of their onset,clinical manifestations,auxiliary examinations and treatment.Results Among the 26 cases,the youngest age of manifestation of mass was 8 days after birth,and the average age was 3 years and 2 months.The peak age was 2-5 years old.Inflammatory mass and toe-finger deformity are the main early clinical manifestations of the disease.These inflammatory masses often lead to hard osteogenic deposits that initially mainly involve the central axis,such as the neck(22/26,84.6%),back(20/26,76.9%),and head(13/26,50%).Toe-finger deformity mainly manifests as symmetrical great toe deformity,or short and deformed thumb and little finger.The diagnosis of FOP requires typical clinical manifestations or ACVR1 gene detection.The main therapeutic drugs for FOP include glucocorticoids and non-steroidal anti-inflammatory drugs.Although not compliant with the recommended medical management of FOP,in our clinical practice children with uncontrollable illness could be treated using a variety of immunosuppressive agents in combination.Conclusions FOP is a rare autosomal dominant heritable disease.The main clinical manifestations observed in this study were recurrent inflammatory mass and toe-finger deformity.If the diagnosis and treatment are not performed in a timely manner,serious complications are likely to affect the prognosis.Therefore,early diagnosis and active treatment should be performed.展开更多
ObjectiveTo describe the clinical manifestations and radiographic characteristics of fibrodysplasia ossificans progressiva (FOP). MethodsThe radiographs and lesion photographs of five patients aged between 23 months a...ObjectiveTo describe the clinical manifestations and radiographic characteristics of fibrodysplasia ossificans progressiva (FOP). MethodsThe radiographs and lesion photographs of five patients aged between 23 months and 17 years diagnosed as FOP were presented and the literatures were reviewed. ResultsClinical features were shortened great toes at birth, episodic soft tissue swellings, pain in the subcutaneous tissues of neck, back, shoulders, and extremities, hard lumps at back and spine, and restricted mobility of neck and arms. Radiological findings included short digit with hallus valgus, scoliosis, exostoses on many bones, and ossification of ligament. The characteristic subcutaneous soft tissues included masses or ossifications of neck, back, extremities, and shoulders. ConclusionThe short terminal phalanges of the thumbs and intermittently progressive heterotopic ossifications of the striated muscles and soft tissues suggest that FOP should promptly get early genetic consultation.展开更多
目的 :研究1例具有非典型临床特征的进行性骨化性纤维增殖不良症(fibrodysplasia ossificans progressiva,FOP)患者,并对其致病基因人活化蛋白/促激蛋白A受体1(activin A type 1 receptor,ACVR1)进行突变分析。方法:根据患者大踇趾轻微...目的 :研究1例具有非典型临床特征的进行性骨化性纤维增殖不良症(fibrodysplasia ossificans progressiva,FOP)患者,并对其致病基因人活化蛋白/促激蛋白A受体1(activin A type 1 receptor,ACVR1)进行突变分析。方法:根据患者大踇趾轻微畸形和进行性异位骨化等临床表现,结合骨骼系统放射线检查、骨ECT和相关血液生化检查进行临床诊断。采集患者、患者父母和60位正常人外周血,提取基因组DNA,对ACVR1基因全部外显子进行聚合酶链反应(polymerase chain reaction,PCR)扩增和序列分析;对突变后的蛋白质结构进行分子模拟以便评估其突变后的功能改变。结果:患者具有非典型的临床表现:先天性大踇趾轻微畸形和进行性非经典顺序的异位骨化,其父母无FOP相关临床表现。患者的ACVR1第5外显子存在c.774 G>C(R258S)杂合突变,而其父母和正常对照组均无此杂合突变。此外,患者和所有正常人都存在c.690 G>A(E230E),此为无意义突变。三维蛋白质分子模拟发现R258与高度保守的甘氨酸-丝氨酸(glycine-serine,GS)活化区邻近,该突变可能导致ACVR1与ACVR1的抑制蛋白FK506结合蛋白12(FK506 binding protein 12,FKBP12)结合的亲和力降低,进而对ACVR1抑制作用降低。结论:典型FOP均在ACVR1之GS区发生突变,而本例FOP在ACVR1激酶区发生突变,这可能是该患者在临床表现呈非典型的原因。该结果有助于我们更好地去理解FOP表型和基因型之间的关系。展开更多
To the Editor:Erythrokeratodermia variabilis (EKV;MIM 133200) is characterized by the coexistence of transient,figurate,erythematous patches,and localized keratotic hyperkeratosis.EKV shows marked phenotypic heterogen...To the Editor:Erythrokeratodermia variabilis (EKV;MIM 133200) is characterized by the coexistence of transient,figurate,erythematous patches,and localized keratotic hyperkeratosis.EKV shows marked phenotypic heterogeneity,even within kindreds bearing the same diseasecausing mutation.[1] The term EKV et progressiva (EKVP) is a severe variant of EKV and has been proposed to encompass the diversity of phenotypes,ranging from limited hyperkeratotic plaques and erythematous patches to severe progressive symmetric erythrokeratodermia which can feature more generalized cutaneous involvement.展开更多
文摘Introduction: Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. Patients and Methods: In the present study, we present a case of FOP with marked progressive ossification of extraskeletal tissues. We investigated whether soluble factors in serum would affect the osteoblast phenotype by examining the effects of serum from this patient and control subjects on mouse osteoblastic MC3T3-E1 cells. Results: The clinical findings of this patient were compatible with FOP, and direct sequence analysis of genomic DNA demonstrated the presence of a heterozygous 617G> A (R206H) mutation of activin type 1 receptor (ACVR1). Serum from the FOP patient enhanced the level of alkaline phosphatase (ALP) in Western blotting, compared with serum from the control, in MC3T3-E1 cells. Moreover, serum from the FOP patient enhanced the levels of ALP, osteocalcin and bone morphogenetic protein-2 mRNA in these cells. Conclusion: We presented a case of FOP with progressive ossification in extra-skeletal tissues with ACVR1 mutation. The present data suggest that the serum from this patient includes some soluble factors, which might enhance the osteoblast differentiation and BMP-2 expression in mouse osteoblastic cells.
文摘Background Fibrodysplasia ossificans progressiva(FOP)is a rare and disabling heritable connective tissue disease that is difficult to treat.This study seeks to explore the clinical characteristics,clinical manifestations,treatment and prognosis of FOP to provide a clinical basis for its early diagnosis and treatment.Methods Twenty-six children with FOP were retrospectively analyzed in terms of their onset,clinical manifestations,auxiliary examinations and treatment.Results Among the 26 cases,the youngest age of manifestation of mass was 8 days after birth,and the average age was 3 years and 2 months.The peak age was 2-5 years old.Inflammatory mass and toe-finger deformity are the main early clinical manifestations of the disease.These inflammatory masses often lead to hard osteogenic deposits that initially mainly involve the central axis,such as the neck(22/26,84.6%),back(20/26,76.9%),and head(13/26,50%).Toe-finger deformity mainly manifests as symmetrical great toe deformity,or short and deformed thumb and little finger.The diagnosis of FOP requires typical clinical manifestations or ACVR1 gene detection.The main therapeutic drugs for FOP include glucocorticoids and non-steroidal anti-inflammatory drugs.Although not compliant with the recommended medical management of FOP,in our clinical practice children with uncontrollable illness could be treated using a variety of immunosuppressive agents in combination.Conclusions FOP is a rare autosomal dominant heritable disease.The main clinical manifestations observed in this study were recurrent inflammatory mass and toe-finger deformity.If the diagnosis and treatment are not performed in a timely manner,serious complications are likely to affect the prognosis.Therefore,early diagnosis and active treatment should be performed.
文摘ObjectiveTo describe the clinical manifestations and radiographic characteristics of fibrodysplasia ossificans progressiva (FOP). MethodsThe radiographs and lesion photographs of five patients aged between 23 months and 17 years diagnosed as FOP were presented and the literatures were reviewed. ResultsClinical features were shortened great toes at birth, episodic soft tissue swellings, pain in the subcutaneous tissues of neck, back, shoulders, and extremities, hard lumps at back and spine, and restricted mobility of neck and arms. Radiological findings included short digit with hallus valgus, scoliosis, exostoses on many bones, and ossification of ligament. The characteristic subcutaneous soft tissues included masses or ossifications of neck, back, extremities, and shoulders. ConclusionThe short terminal phalanges of the thumbs and intermittently progressive heterotopic ossifications of the striated muscles and soft tissues suggest that FOP should promptly get early genetic consultation.
文摘目的 :研究1例具有非典型临床特征的进行性骨化性纤维增殖不良症(fibrodysplasia ossificans progressiva,FOP)患者,并对其致病基因人活化蛋白/促激蛋白A受体1(activin A type 1 receptor,ACVR1)进行突变分析。方法:根据患者大踇趾轻微畸形和进行性异位骨化等临床表现,结合骨骼系统放射线检查、骨ECT和相关血液生化检查进行临床诊断。采集患者、患者父母和60位正常人外周血,提取基因组DNA,对ACVR1基因全部外显子进行聚合酶链反应(polymerase chain reaction,PCR)扩增和序列分析;对突变后的蛋白质结构进行分子模拟以便评估其突变后的功能改变。结果:患者具有非典型的临床表现:先天性大踇趾轻微畸形和进行性非经典顺序的异位骨化,其父母无FOP相关临床表现。患者的ACVR1第5外显子存在c.774 G>C(R258S)杂合突变,而其父母和正常对照组均无此杂合突变。此外,患者和所有正常人都存在c.690 G>A(E230E),此为无意义突变。三维蛋白质分子模拟发现R258与高度保守的甘氨酸-丝氨酸(glycine-serine,GS)活化区邻近,该突变可能导致ACVR1与ACVR1的抑制蛋白FK506结合蛋白12(FK506 binding protein 12,FKBP12)结合的亲和力降低,进而对ACVR1抑制作用降低。结论:典型FOP均在ACVR1之GS区发生突变,而本例FOP在ACVR1激酶区发生突变,这可能是该患者在临床表现呈非典型的原因。该结果有助于我们更好地去理解FOP表型和基因型之间的关系。
文摘To the Editor:Erythrokeratodermia variabilis (EKV;MIM 133200) is characterized by the coexistence of transient,figurate,erythematous patches,and localized keratotic hyperkeratosis.EKV shows marked phenotypic heterogeneity,even within kindreds bearing the same diseasecausing mutation.[1] The term EKV et progressiva (EKVP) is a severe variant of EKV and has been proposed to encompass the diversity of phenotypes,ranging from limited hyperkeratotic plaques and erythematous patches to severe progressive symmetric erythrokeratodermia which can feature more generalized cutaneous involvement.
