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Novel mutations in the C-terminal region of GMPPB causing limb-girdle muscular dystrophy overlapping with congenital myasthenic syndrome 期刊论文

编号：

18a77fa9-2e5c-4c2e-a17d-f09a2c287129
作者：

Luo, Sushan(罗苏珊)#^[1]Cai, Shuang(蔡爽)^[1]Maxwell, Susan^[2];Yue, Dongyue^[3];Zhu, Wenhua(朱雯华)^[1]Qiao, Kai^[4];Zhu, Zhen^[5];Zhou, Lei(周磊)^[1]Xi, Jianying(奚剑英)^[1]Lu, Jiahong(卢家红)^[1]Beeson, David^[2];Zhao, Chongbo^[1,3];
语种：

English
期刊：

NEUROMUSCULAR DISORDERS ISSN：0960-8966 2017 年 27 卷 6 期 (557 - 564) ; JUN
收录：
关键词：

Limb girdle muscular dystrophy Congenital myasthenic syndrome GMPPB Mutation hotspot Muscle MRI
摘要：

Mutations in the GMPPB gene may underlie both limb girdle muscular dystrophy (LGMD) and congenital myasthenic syndrome (CMS). Forty-one cases have been reported to date and hotspot mutations are emerging in the Caucasian population. Clinical and pathological features of 5 patients with compound heterozygous GMPPB mutations were collected and retrospectively reviewed. In vitro functional analysis was performed to investigate the pathogeneity of GMPPB variants. The patients presented with proximal limb weakness in their first to second decades. Fluctuating muscle weakness, myalgia and calf hypertrophy were the major complaints. Myogenic changes on electromyography and marked attenuation on 3 Hz repetitive nerve stimulation were observed in all patients. Four reported a beneficial response to pyridostigmine. Muscle MRI showed selective involvement in the calf in case 1. Immunolabeling of a-dystroglycan was abnormal for case 1 and case 2. Four novel missense mutations in the C-terminal region of GMPPB were identified, with p.(Arg357His) being present in all the cases. In vitro functional assays demonstrated that these variants did not markedly reduce the amount of GMPPB, but gave rise to an increased propensity for protein aggregation. Increasingly, patients with GMPPB mutations are found to present with an overlapping LGMD/myasthenic syndrome. The mutation spectrum in Chinese patients may differ from that of European populations, with the mutation p.(Arg357His) most frequently found. These mutations may lead to abnormal folding of GMPPB leading to protein aggregates in the cytoplasm rather than an overall loss in protein expression. (C) 2017 Elsevier B.V. All rights reserved.
推荐引用方式
GB/T 7714：

Luo Sushan,Cai Shuang,Maxwell Susan, et al. Novel mutations in the C-terminal region of GMPPB causing limb-girdle muscular dystrophy overlapping with congenital myasthenic syndrome [J].NEUROMUSCULAR DISORDERS,2017,27(6):557-564.
APA：

Luo Sushan,Cai Shuang,Maxwell Susan,Yue Dongyue,&Zhao Chongbo.(2017).Novel mutations in the C-terminal region of GMPPB causing limb-girdle muscular dystrophy overlapping with congenital myasthenic syndrome .NEUROMUSCULAR DISORDERS,27(6):557-564.
MLA：

Luo Sushan, et al. "Novel mutations in the C-terminal region of GMPPB causing limb-girdle muscular dystrophy overlapping with congenital myasthenic syndrome" .NEUROMUSCULAR DISORDERS 27,6(2017):557-564.

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