Clinical and Genetic Features of Chinese X-linked Charcot-Marie-Tooth Type 1 Disease.
Clinical and Genetic Features of Chinese X-linked Charcot-Marie-Tooth Type 1 Disease.
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DOI：
10.4103/0366-6999.204925
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发表时间：
2017-05-05
影响因子：
6.1
通讯作者：
Yuan Y
中科院分区：
文献类型：
--
作者：
Lu YY;Lyu H;Jin SQ;Zuo YH;Liu J;Wang ZX;Zhang W;Yuan Y
X连锁腓骨肌萎缩症1型（CMT 1X）是由差距连接β-1蛋白（GJB 1）基因（也称为连接蛋白32）突变引起的遗传性神经病的最常见形式之一。本研究介绍了一系列中国人GJB 1基因突变患者的临床和遗传学特征。2005年1月至2016年1月北京大学第一医院神经内科收治的22例无亲缘关系的患者，均被鉴定为GJB 1突变。他们的临床记录和实验室检查结果进行了回顾性收集和审查。通过靶向下一代测序（NGS）分析GJB 1基因中的突变。用桑格测序确认核苷酸改变。CMT 1X患者主要表现为下肢远端肌无力伴轻度感觉障碍。平均发病年龄为15.6 ± 8.7岁（1岁至42岁）。4例患者（18.2%）突然出现脑部症状，2例为首发症状。1例有持续的中枢神经系统（CNS）体征。有19种不同的杂合突变，包括15种已知突变和4种新突变（c.115G>T、c.380T>A、c.263C>A和c.818_819insGGGCT）。在22例中国CMT 1X患者中，GJB 1突变频率为跨膜结构域1（TM 1）4.5%，TM 2 4.5%，TM 3 22.7%，TM 4 9.1%，细胞外1（EC 1）4.5%，EC 2 27.3%，胞内环9.1%，N端结构域13.6%，C端结构域为4.5%。这些患者中有5例（22.7%）出现CMT 1X伴CNS损伤。这项研究表明，CNS损害在中国CMT 1X患者中并不罕见。GJB 1基因的EC2区突变是中国CMT 1X患者的突变热点。
X-linked Charcot-Marie-Tooth type 1 (CMT1X) disease is one of the most common forms of inherited neuropathy caused by mutations in the gap junction beta-1 protein (GJB1) gene (also known as connexin 32). This study presented the clinical and genetic features of a series of Chinese patients with GJB1 gene mutations. A total of 22 patients from unrelated families, who were referred to Department of Neurology, Peking University First Hospital from January 2005 to January 2016, were identified with GJB1 mutations. Their clinical records and laboratory findings were retrospectively collected and reviewed. Mutations in the GJB1 gene were analyzed by targeted next-generation sequencing (NGS). Nucleotide alternations were confirmed with Sanger sequencing. The CMT1X patients predominantly showed distal muscle weakness of lower limbs with mild sensory disturbance. The mean age of onset was 15.6 ± 8.7 years (ranging from 1 year to 42 years). The sudden onset of cerebral symptoms appeared in four patients (18.2%); two were initial symptoms. One case had constant central nervous system (CNS) signs. There were 19 different heterozygous mutations, including 15 known mutations and four novel mutations (c.115G>T, c.380T>A, c.263C>A, and c.818_819insGGGCT). Among the 22 Chinese patients with CMT1X, the frequency of the GJB1 mutation was 4.5% in transmembrane domain 1 (TM1), 4.5% in TM2, 22.7% in TM3, 9.1% in TM4, 4.5% in extracellular 1 (EC1), 27.3% in EC2, 9.1% in intracellular loop, 13.6% in the N-terminal domain, and 4.5% in the C-terminal domain. CMT1X with CNS impairment appeared in five (22.7%) of these patients. This study indicated that CNS impairment was not rare in Chinese CMT1X patients. Mutations in the EC2 domain of the GJB1 gene were hotspot in Chinese CMT1X patients.