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Mechanisms of Congenital Myasthenia Caused by Three Mutations in the COLQ Gene

The gene encoding collagen like tail subunit of asymmetric acetylcholinesterase (COLQ) is responsible for the transcription of three strands of collagen of acetylcholinesterase, which is attached to the endplate of neuromuscular junctions. Mutations in the COLQ gene are inherited in an autosomal-rec...

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Autores principales: Luo, Xiaona, Wang, Chunmei, Lin, Longlong, Yuan, Fang, Wang, Simei, Wang, Yilin, Wang, Anqi, Wang, Chao, Wu, Shengnan, Lan, Xiaoping, Xu, Quanmei, Yin, Rongrong, Cheng, Hongyi, Zhang, Yuanfeng, Xi, Jiaming, Zhang, Jie, Sun, Xiaomin, Yan, Jingbin, Zeng, Fanyi, Chen, Yucai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8667818/
https://www.ncbi.nlm.nih.gov/pubmed/34912755
http://dx.doi.org/10.3389/fped.2021.679342
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author Luo, Xiaona
Wang, Chunmei
Lin, Longlong
Yuan, Fang
Wang, Simei
Wang, Yilin
Wang, Anqi
Wang, Chao
Wu, Shengnan
Lan, Xiaoping
Xu, Quanmei
Yin, Rongrong
Cheng, Hongyi
Zhang, Yuanfeng
Xi, Jiaming
Zhang, Jie
Sun, Xiaomin
Yan, Jingbin
Zeng, Fanyi
Chen, Yucai
author_facet Luo, Xiaona
Wang, Chunmei
Lin, Longlong
Yuan, Fang
Wang, Simei
Wang, Yilin
Wang, Anqi
Wang, Chao
Wu, Shengnan
Lan, Xiaoping
Xu, Quanmei
Yin, Rongrong
Cheng, Hongyi
Zhang, Yuanfeng
Xi, Jiaming
Zhang, Jie
Sun, Xiaomin
Yan, Jingbin
Zeng, Fanyi
Chen, Yucai
author_sort Luo, Xiaona
collection PubMed
description The gene encoding collagen like tail subunit of asymmetric acetylcholinesterase (COLQ) is responsible for the transcription of three strands of collagen of acetylcholinesterase, which is attached to the endplate of neuromuscular junctions. Mutations in the COLQ gene are inherited in an autosomal-recessive manner and can lead to type V congenital myasthenia syndrome (CMS), which manifests as decreased muscle strength at birth or shortly after birth, respiratory failure, restricted eye movements, drooping of eyelids, and difficulty swallowing. Here we reported three variants within COLQ in two unrelated children with CMS. An intronic variant (c.393+1G>A) and a novel missense variant (p.Q381P) were identified as compound heterozygous in a 13-month-old boy, with the parents being carriers of each. An intragenic deletion including exons 14 and 15 was found in a homozygous state in a 12-year-old boy. We studied the relative expression of the COLQ and AChE gene in the probands' families, performed three-dimensional protein structural analysis, and analyzed the conservation of the missense mutation c.1142A>C (p.Q381P). The splicing mutation c.393+1G>A was found to affect the normal splicing of COLQ exon 5, resulting in a 27-bp deletion. The missense mutation c.1142A>C (p.Q381P) was located in a conserved position in different species. We found that homozygous deletion of COLQ exons 14–15 resulted in a 241-bp deletion, which decreased the number of amino acids and caused a frameshift translation. COLQ expression was significantly lower in the probands than in the probands' parents and siblings, while AChE expression was significantly higher. Moreover, the mutations were found to cause significant differences in the predicted three-dimensional structure of the protein. The splicing mutation c.393+1G>A, missense mutation c.1A>C (p.Q381P), and COLQ exon 14–15 deletion could cause CMS.
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spelling pubmed-86678182021-12-14 Mechanisms of Congenital Myasthenia Caused by Three Mutations in the COLQ Gene Luo, Xiaona Wang, Chunmei Lin, Longlong Yuan, Fang Wang, Simei Wang, Yilin Wang, Anqi Wang, Chao Wu, Shengnan Lan, Xiaoping Xu, Quanmei Yin, Rongrong Cheng, Hongyi Zhang, Yuanfeng Xi, Jiaming Zhang, Jie Sun, Xiaomin Yan, Jingbin Zeng, Fanyi Chen, Yucai Front Pediatr Pediatrics The gene encoding collagen like tail subunit of asymmetric acetylcholinesterase (COLQ) is responsible for the transcription of three strands of collagen of acetylcholinesterase, which is attached to the endplate of neuromuscular junctions. Mutations in the COLQ gene are inherited in an autosomal-recessive manner and can lead to type V congenital myasthenia syndrome (CMS), which manifests as decreased muscle strength at birth or shortly after birth, respiratory failure, restricted eye movements, drooping of eyelids, and difficulty swallowing. Here we reported three variants within COLQ in two unrelated children with CMS. An intronic variant (c.393+1G>A) and a novel missense variant (p.Q381P) were identified as compound heterozygous in a 13-month-old boy, with the parents being carriers of each. An intragenic deletion including exons 14 and 15 was found in a homozygous state in a 12-year-old boy. We studied the relative expression of the COLQ and AChE gene in the probands' families, performed three-dimensional protein structural analysis, and analyzed the conservation of the missense mutation c.1142A>C (p.Q381P). The splicing mutation c.393+1G>A was found to affect the normal splicing of COLQ exon 5, resulting in a 27-bp deletion. The missense mutation c.1142A>C (p.Q381P) was located in a conserved position in different species. We found that homozygous deletion of COLQ exons 14–15 resulted in a 241-bp deletion, which decreased the number of amino acids and caused a frameshift translation. COLQ expression was significantly lower in the probands than in the probands' parents and siblings, while AChE expression was significantly higher. Moreover, the mutations were found to cause significant differences in the predicted three-dimensional structure of the protein. The splicing mutation c.393+1G>A, missense mutation c.1A>C (p.Q381P), and COLQ exon 14–15 deletion could cause CMS. Frontiers Media S.A. 2021-11-29 /pmc/articles/PMC8667818/ /pubmed/34912755 http://dx.doi.org/10.3389/fped.2021.679342 Text en Copyright © 2021 Luo, Wang, Lin, Yuan, Wang, Wang, Wang, Wang, Wu, Lan, Xu, Yin, Cheng, Zhang, Xi, Zhang, Sun, Yan, Zeng and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Luo, Xiaona
Wang, Chunmei
Lin, Longlong
Yuan, Fang
Wang, Simei
Wang, Yilin
Wang, Anqi
Wang, Chao
Wu, Shengnan
Lan, Xiaoping
Xu, Quanmei
Yin, Rongrong
Cheng, Hongyi
Zhang, Yuanfeng
Xi, Jiaming
Zhang, Jie
Sun, Xiaomin
Yan, Jingbin
Zeng, Fanyi
Chen, Yucai
Mechanisms of Congenital Myasthenia Caused by Three Mutations in the COLQ Gene
title Mechanisms of Congenital Myasthenia Caused by Three Mutations in the COLQ Gene
title_full Mechanisms of Congenital Myasthenia Caused by Three Mutations in the COLQ Gene
title_fullStr Mechanisms of Congenital Myasthenia Caused by Three Mutations in the COLQ Gene
title_full_unstemmed Mechanisms of Congenital Myasthenia Caused by Three Mutations in the COLQ Gene
title_short Mechanisms of Congenital Myasthenia Caused by Three Mutations in the COLQ Gene
title_sort mechanisms of congenital myasthenia caused by three mutations in the colq gene
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8667818/
https://www.ncbi.nlm.nih.gov/pubmed/34912755
http://dx.doi.org/10.3389/fped.2021.679342
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