Congenital Myasthenic Syndrome due to DOK7 mutations in a family from Chile.
Congenital Myasthenic Syndrome due to DOK7 mutations in a family from Chile.
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DOI：
10.4081/ejtm.2017.6832
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发表时间：
2017-06-27
影响因子：
2.2
通讯作者：
Maselli RA
中科院分区：
文献类型：
--
作者：
Bevilacqua JA;Lara M;Díaz J;Campero M;Vázquez J;Maselli RA
先天性肌无力综合征（CMS）是由编码神经肌肉接头蛋白的基因突变引起的神经肌肉传递障碍。一位61岁的女性和她的姐姐从小就表现出双侧上睑下垂，面部和近端肢体无力，脊柱侧凸。另一名女性兄弟姐妹的症状较轻，而其他家庭成员则无症状。先证者重复刺激面神经，肌肉反应减弱。单纤维肌电图显示抖动和阻滞增加。肌肉活检显示2型纤维萎缩，无管状聚集。三个受影响同胞的突变分析揭示了DOK 7中的两个复合杂合突变：c.1457delC，预测p.Pro486Argfs*13并截断蛋白质C末端结构域，以及c.473G>A，预测p.Arg158Gln并破坏磷酸酪氨酸结合（PTB）结构域中的dok 7-MuSK相互作用。未受影响的家庭成员只携带一种或两种突变。讨论其中两名受影响的姐妹篇在沙丁胺醇治疗后表现出明显的改善，这说明了正确诊断和治疗DOK 7-CMS的益处。
Congenital myasthenic syndromes (CMS) are neuromuscular transmission disorders caused by mutations in genes encoding neuromuscular junction proteins. A 61-year-old female and her older sister showed bilateral ptosis, facial and proximal limb weakness, and scoliosis since childhood. Another female sibling had milder signs, while other family members were asymptomatic. Facial nerve repetitive stimulation in the proband showed decrement of muscle responses. Single fiber EMG revealed increased jitter and blocking. Muscle biopsy showed type 2-fiber atrophy, without tubular aggregates. Mutational analysis in the three affected siblings revealed two compound heterozygous mutations in DOK7: c.1457delC, that predicts p.Pro486Argfs*13 and truncates the protein C-terminal domain, and c.473G>A, that predicts p.Arg158Gln and disruption of the dok7-MuSK interaction in the phosphotyrosine binding (PTB) domain. Unaffected family members carried only one or neither mutation. Discussion. Two of the affected sisters showed marked improvement with salbutamol treatment, which illustrates the benefits of a correct diagnosis and treatment of DOK7-CMS.