CAJ | 학술논문

目的报道1例中国人常染色体显性遗传进行性骨化性纤维发育不良患者的临床特征,并对其致病基因ACVR1进行突变研究.方法根据患儿的临床症状、体征、骨骼系统放射线检查和相关血液生化检查进行临床诊断.采集患儿及其父母外周血,提取DNA,PCR扩增ACVR1基因第4外显子,测序检测突变.结果患儿女,3岁,临床表现先天性双侧拇趾畸形和进行性软组织异位性骨化,X线片示颈后和脊柱旁软组织多发不规则骨化影.其母双侧拇趾粗大外翻,但无异位骨性结节.家族其他人员无相关病史.PCR扩增片段直接测序,显示患儿ACVR1基因第4外显子c617发生G＞A颠换(R206H),其父母ACVR1基因均未检测到该突变.结论该病例有典型的进行性骨化性纤维发育不良的临床表现,为中国内地首例用基因方法确诊的病例,基因分析确定为新生突变,与国外报道的相同.
목적 보도1례중국인상염색체현성유전진행성골화성섬유발육불량환자적림상특정,병대기치병기인ACVR1진행돌변연구.방법 근거환인적림상증상、체정、골격계통방사선검사화상관혈액생화검사진행림상진단.채집환인급기부모외주혈,제취DNA,PCR확증ACVR1기인제4외현자,측서검측돌변.결과 환인녀,3세,림상표현선천성쌍측무지기형화진행성연조직이위성골화,X선편시경후화척주방연조직다발불규칙골화영.기모쌍측무지조대외번,단무이위골성결절.가족기타인원무상관병사.PCR확증편단직접측서,현시환인ACVR1기인제4외현자c617발생G＞A전환(R206H),기부모ACVR1기인균미검측도해돌변.결론 해병례유전형적진행성골화성섬유발육불량적림상표현,위중국내지수례용기인방법학진적병례,기인분석학정위신생돌변,여국외보도적상동.
Objective Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant inherited disease caused by mutations of ACVR1 gene and can be inherited from either mother or father.FOP is characterized by the presence of malformations of the big toes and of progressive extra-skeletal ossification.Direct sequence analyses of genomic DNA have demonstrated that there is an identical single nucleotide substitution (c617G→A,R206H) in the glycine-serine (GS) activation domain of ACVR1 gene,responsible for all affected individuals reported so far.We report a Chinese girl with typical FOP characteristics.in whom the same mutation in ACVR1 was identified.Methods Clinical diagnosis was based on physical examination,radiological findings,and biochemical tests.For mutation detection,peripheral blood was obtained with informed consent from the patient and the parents.Genomic DNA was extracted from peripheral blood using standard method.Exon 4 of ACVR1 was amplified by polymerase chain reaction (PCR),and the PCR products were subjected to automatic DNA sequencing.Results The affected girl is 3-year-old and showed typical clinical manifestations of FOP.She had malformations of the halluces at birth and subsequently progressive extra-skeletal ossification developed at the age of 8-9 months.Then,she gradually developed stiffness of the knee joint and neck but remained ambulant.Radiographic changes were observable.e.g.,the extra-skeletal ossification was found at cervical spine.Her mother has congenital malformations of the halluces.but had no postnatal progressive extra-skeletal ossification.Her father and other family members are normal.With direct sequencing of the PCR products.a G to A substitution at c617 of ACVR1 (R206H) was detected in the patient only but not in her parents.Paternity analysis suggested that it is a de novo mutation.Conclusion This is the first case reported in a Chinese patient with FOP in the mainland of China.which was confirmed by direct sequencing.Although sporadic cases of FOP have been reported in diverse geographic and ethnic group,the mutations of ACVR1 c617 (R206H) are identical up to now.The presence of mutation hot spot facilitates molecular diagnosis in clinical practice.Genetic detection is important for FOP patients to avoid misdiagnosis and further damages.