Department of Neurology and Research Center of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350004, China.
Chin Med J (Engl). 2017 Oct 5;130(19):2273-2278. doi: 10.4103/0366-6999.215338.
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive neuromuscular diseases resulting from dystrophin (DMD) gene mutations. It has been known that the carrier of DMD mutations may also have symptoms of the disease. While de novo mutation is quite common in BMD/DMD patients, it is rarely reported in the female carriers.
Two sporadic Chinese patients with progressive muscular dystrophy and their familial members were recruited. The targeted next-generation sequencing (NGS) and the multiplex ligation-dependent probe analysis (MLPA) were performed in the proband. Blood tests, electrocardiography, echocardiography, and electromyography were also evaluated.
Two novel mutations of DMD gene were identified, c.7318C>T (p.Q2440*) in the male proband and c.4983dupA (p.A1662Sfs*24) in the female carrier. The MLPA analysis did not detect any large rearrangements. The haplotype analysis indicated that the two mutations were derived from de novo mutagenesis.
We identified two novel de novo mutations of DMD gene in two Chinese pedigrees, one of which caused a female patient with muscular dystrophy. The mutational analysis is important for DMD patients and carriers in the absence of a family history. The NGS can help detect the mutations in MLPA-negative patients.
杜氏肌营养不良症（DMD）和贝克肌营养不良症（BMD）是由肌营养不良蛋白（DMD）基因突变引起的 X 连锁隐性神经肌肉疾病。已知 DMD 突变的携带者也可能有该疾病的症状。虽然从头突变在 BMD/DMD 患者中很常见，但在女性携带者中很少报道。
招募了两名患有进行性肌营养不良症的散发性中国患者及其家族成员。对先证者进行靶向下一代测序（NGS）和多重连接依赖性探针分析（MLPA）。还进行了血液检查、心电图、超声心动图和肌电图检查。
在男性先证者中发现了 DMD 基因的两个新突变，c.7318C>T（p.Q2440*），在女性携带者中发现了 c.4983dupA（p.A1662Sfs*24）。MLPA 分析未检测到任何大片段重排。单倍型分析表明，这两个突变是从头突变引起的。
我们在两个中国家系中鉴定了 DMD 基因的两个新的从头突变，其中一个导致了一名患有肌营养不良症的女性患者。突变分析对于无家族史的 DMD 患者和携带者很重要。NGS 可帮助检测 MLPA 阴性患者的突变。
Zotero 插件