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Congenital myasthenic syndrome in China: genetic and myopathological characterization

OBJECTIVE: We aimed to summarize the clinical, genetic, and myopathological features of a cohort of Chinese patients with congenital myasthenic syndrome, and follow up on therapeutic outcomes. METHODS: The clinical spectrum, mutational frequency of genes, and pathological diagnostic clues of various...

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Autores principales: Zhao, Yawen, Li, Ying, Bian, Yang, Yao, Sheng, Liu, Penju, Yu, Meng, Zhang, Wei, Wang, Zhaoxia, Yuan, Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045908/
https://www.ncbi.nlm.nih.gov/pubmed/33756069
http://dx.doi.org/10.1002/acn3.51346
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author Zhao, Yawen
Li, Ying
Bian, Yang
Yao, Sheng
Liu, Penju
Yu, Meng
Zhang, Wei
Wang, Zhaoxia
Yuan, Yun
author_facet Zhao, Yawen
Li, Ying
Bian, Yang
Yao, Sheng
Liu, Penju
Yu, Meng
Zhang, Wei
Wang, Zhaoxia
Yuan, Yun
author_sort Zhao, Yawen
collection PubMed
description OBJECTIVE: We aimed to summarize the clinical, genetic, and myopathological features of a cohort of Chinese patients with congenital myasthenic syndrome, and follow up on therapeutic outcomes. METHODS: The clinical spectrum, mutational frequency of genes, and pathological diagnostic clues of various subtypes of patients with congenital myasthenic syndrome were summarized. Therapeutic effects were followed up. RESULTS: Thirty‐five patients from 29 families were recruited. Ten genes were identified: GFPT1 (27.6%), AGRN (17.2%), CHRNE (17.2%), COLQ (13.8%), GMPPB (6.9%), CHAT, CHRNA1, DOK7, COG7, and SLC25A1 (3.4% each, respectively). Sole limb‐girdle weakness was found in patients with AGRN (1/8) and GFPT1 (7/8) mutations, whereas distal weakness was all observed in patients with AGRN (6/8) mutations. Tubular aggregates were only found in patients with GFPT1 mutations (5/6). The patients with GMPPB mutations (2/2) had decreased alpha‐dystroglycan. Acetylcholinesterase inhibitor therapy resulted in no response or worsened symptoms in patients with COLQ mutations, a diverse response in patients with AGRN mutations, and a good response in patients with other subtypes. Albuterol therapy was effective or harmless in most subtypes. Therapy effects became attenuated with long‐term use in patients with COLQ or AGRN mutations. INTERPRETATION: The genetic distribution of congenital myasthenic syndrome in China is distinct from that of other ethnic origins. The appearance of distal weakness, selective limb‐girdle myasthenic syndrome, tubular aggregates, and decreased alpha‐dystroglycan were indicative of the specific subtypes. Based on the follow‐up findings, we suggest cautious evaluation of the long‐term efficacy of therapeutic agents in congenital myasthenic syndrome.
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spelling pubmed-80459082021-04-16 Congenital myasthenic syndrome in China: genetic and myopathological characterization Zhao, Yawen Li, Ying Bian, Yang Yao, Sheng Liu, Penju Yu, Meng Zhang, Wei Wang, Zhaoxia Yuan, Yun Ann Clin Transl Neurol Research Articles OBJECTIVE: We aimed to summarize the clinical, genetic, and myopathological features of a cohort of Chinese patients with congenital myasthenic syndrome, and follow up on therapeutic outcomes. METHODS: The clinical spectrum, mutational frequency of genes, and pathological diagnostic clues of various subtypes of patients with congenital myasthenic syndrome were summarized. Therapeutic effects were followed up. RESULTS: Thirty‐five patients from 29 families were recruited. Ten genes were identified: GFPT1 (27.6%), AGRN (17.2%), CHRNE (17.2%), COLQ (13.8%), GMPPB (6.9%), CHAT, CHRNA1, DOK7, COG7, and SLC25A1 (3.4% each, respectively). Sole limb‐girdle weakness was found in patients with AGRN (1/8) and GFPT1 (7/8) mutations, whereas distal weakness was all observed in patients with AGRN (6/8) mutations. Tubular aggregates were only found in patients with GFPT1 mutations (5/6). The patients with GMPPB mutations (2/2) had decreased alpha‐dystroglycan. Acetylcholinesterase inhibitor therapy resulted in no response or worsened symptoms in patients with COLQ mutations, a diverse response in patients with AGRN mutations, and a good response in patients with other subtypes. Albuterol therapy was effective or harmless in most subtypes. Therapy effects became attenuated with long‐term use in patients with COLQ or AGRN mutations. INTERPRETATION: The genetic distribution of congenital myasthenic syndrome in China is distinct from that of other ethnic origins. The appearance of distal weakness, selective limb‐girdle myasthenic syndrome, tubular aggregates, and decreased alpha‐dystroglycan were indicative of the specific subtypes. Based on the follow‐up findings, we suggest cautious evaluation of the long‐term efficacy of therapeutic agents in congenital myasthenic syndrome. John Wiley and Sons Inc. 2021-03-23 /pmc/articles/PMC8045908/ /pubmed/33756069 http://dx.doi.org/10.1002/acn3.51346 Text en © 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Zhao, Yawen
Li, Ying
Bian, Yang
Yao, Sheng
Liu, Penju
Yu, Meng
Zhang, Wei
Wang, Zhaoxia
Yuan, Yun
Congenital myasthenic syndrome in China: genetic and myopathological characterization
title Congenital myasthenic syndrome in China: genetic and myopathological characterization
title_full Congenital myasthenic syndrome in China: genetic and myopathological characterization
title_fullStr Congenital myasthenic syndrome in China: genetic and myopathological characterization
title_full_unstemmed Congenital myasthenic syndrome in China: genetic and myopathological characterization
title_short Congenital myasthenic syndrome in China: genetic and myopathological characterization
title_sort congenital myasthenic syndrome in china: genetic and myopathological characterization
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045908/
https://www.ncbi.nlm.nih.gov/pubmed/33756069
http://dx.doi.org/10.1002/acn3.51346
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