Abstract:

Objective  To summarize the phenotype and genotype of a family of Becker muscular dystrophy (BMD) caused by a novel missense mutation of DMD gene. Methods and Results Clinical data of one BMD proband and the family members were collected. Next-generation sequencing technology was used to detect possible gene mutation in the proband, a 25-year-old male BMD patient. Sanger sequencing technology was used to further detect possible mutation of c.4449T > G (p.Asn1483Lys) locus of DMD gene in the proband's mother and younger sister. The analysis was carried out combined with clinical data of the proband and other family members. Results showed the patient had the same phenotype as his two uncles (mother's brothers), who presented pseudohypertrophy of calf muscles, atrophy and weakness of proximal lower extremities and elevated serum creatine kinase (CK). Gene mutation analysis demonstrated a novel missense mutation c.4449T > G (p.Asn1483Lys) in exon 34 of DMD gene in the proband. The proband's mother and younger sister were carriers of mutated gene. Combined with the clinical manifestations of proband's uncles, the patient was clearly diagnosed as BMD, and the family was clearly diagnosed as BMD pedigree. Besides, there was a common separation phenomenon in the family. Conclusions The study described a novel missense mutation in exon 34 c.4449T > G (p.Asn1483Lys) of DMD gene which caused BMD. This enriches the mutation map of DMD gene, and also provides valuable information for genetic counseling and prenatal diagnosis.

Key words: Muscular dystrophy, Duchenne, Genes, Mutation, missense, Pedigree

摘要：

目的 总结 DMD 基因新发错义突变导致的 Becker 型肌营养不良症一家系临床表型及基因突变特点。方法与结果 采用第二代测序技术对 1 例 25 岁男性 Becker 型肌营养不良症患者进行基因检测，Sanger测序进一步验证患者之母和妹 DMD 基因 c.4449T > G（p.Asn1483Lys）位点，并结合患者及其家族成员的临床资料进行分析。结果显示，患者及其两位舅父具有相同的临床表型，双小腿肌肉呈假性肥大，双下肢近端肌萎缩和肌无力，血清肌酸激酶水平升高。患者基因检测 DMD 基因外显子 34 c.4449T > G（p.Asn1483Lys）为错义突变，经检索为新发突变，其母和妹为携带者，结合患者两位舅父临床表现，确诊为 Becker型肌营养不良症，该家系为 Becker型肌营养不良症家系且存在该基因突变位点的共分离现象。结论 DMD 基因外显子34 c.4449T > G（p.Asn1483Lys）为新发错义突变，丰富了 DMD 基因突变谱，为该家系遗传咨询和产前诊断提供了有价值的信息。

关键词: 肌营养不良, 杜氏, 基因, 突变, 误义, 系谱