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MET mutation causes muscular dysplasia and arthrogryposis

Arthrogryposis is a group of phenotypically and genetically heterogeneous disorders characterized by congenital contractures of two or more parts of the body; the pathogenesis and the causative genes of arthrogryposis remain undetermined. We examined a four‐generation arthrogryposis pedigree charact...

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Autores principales: Zhou, Hang, Lian, Chengjie, Wang, Tingting, Yang, Xiaoming, Xu, Caixia, Su, Deying, Zheng, Shuhui, Huang, Xiangyu, Liao, Zhiheng, Zhou, Taifeng, Qiu, Xianjian, Chen, Yuyu, Gao, Bo, Li, Yongyong, Wang, Xudong, You, Guoling, Fu, Qihua, Gurnett, Christina, Huang, Dongsheng, Su, Peiqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404111/
https://www.ncbi.nlm.nih.gov/pubmed/30777867
http://dx.doi.org/10.15252/emmm.201809709
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author Zhou, Hang
Lian, Chengjie
Wang, Tingting
Yang, Xiaoming
Xu, Caixia
Su, Deying
Zheng, Shuhui
Huang, Xiangyu
Liao, Zhiheng
Zhou, Taifeng
Qiu, Xianjian
Chen, Yuyu
Gao, Bo
Li, Yongyong
Wang, Xudong
You, Guoling
Fu, Qihua
Gurnett, Christina
Huang, Dongsheng
Su, Peiqiang
author_facet Zhou, Hang
Lian, Chengjie
Wang, Tingting
Yang, Xiaoming
Xu, Caixia
Su, Deying
Zheng, Shuhui
Huang, Xiangyu
Liao, Zhiheng
Zhou, Taifeng
Qiu, Xianjian
Chen, Yuyu
Gao, Bo
Li, Yongyong
Wang, Xudong
You, Guoling
Fu, Qihua
Gurnett, Christina
Huang, Dongsheng
Su, Peiqiang
author_sort Zhou, Hang
collection PubMed
description Arthrogryposis is a group of phenotypically and genetically heterogeneous disorders characterized by congenital contractures of two or more parts of the body; the pathogenesis and the causative genes of arthrogryposis remain undetermined. We examined a four‐generation arthrogryposis pedigree characterized by camptodactyly, limited forearm supination, and loss of myofibers in the forearms and hands. By using whole‐exome sequencing, we confirmed MET p.Y1234C mutation to be responsible for arthrogryposis in this pedigree. MET p.Y1234C mutation caused the failure of activation of MET tyrosine kinase. A Met p.Y1232C mutant mouse model was established. The phenotypes of homozygous mice included embryonic lethality and complete loss of muscles that originated from migratory precursors. Heterozygous mice were born alive and showed reduction of the number of myofibers in both appendicular and axial muscles. Defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts were proven to be responsible for the skeletal muscle dysplasia of mutant mice. Overall, our study shows MET to be a causative gene of arthrogryposis and MET mutation could cause skeletal muscle dysplasia in human beings.
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spelling pubmed-64041112019-03-18 MET mutation causes muscular dysplasia and arthrogryposis Zhou, Hang Lian, Chengjie Wang, Tingting Yang, Xiaoming Xu, Caixia Su, Deying Zheng, Shuhui Huang, Xiangyu Liao, Zhiheng Zhou, Taifeng Qiu, Xianjian Chen, Yuyu Gao, Bo Li, Yongyong Wang, Xudong You, Guoling Fu, Qihua Gurnett, Christina Huang, Dongsheng Su, Peiqiang EMBO Mol Med Report Arthrogryposis is a group of phenotypically and genetically heterogeneous disorders characterized by congenital contractures of two or more parts of the body; the pathogenesis and the causative genes of arthrogryposis remain undetermined. We examined a four‐generation arthrogryposis pedigree characterized by camptodactyly, limited forearm supination, and loss of myofibers in the forearms and hands. By using whole‐exome sequencing, we confirmed MET p.Y1234C mutation to be responsible for arthrogryposis in this pedigree. MET p.Y1234C mutation caused the failure of activation of MET tyrosine kinase. A Met p.Y1232C mutant mouse model was established. The phenotypes of homozygous mice included embryonic lethality and complete loss of muscles that originated from migratory precursors. Heterozygous mice were born alive and showed reduction of the number of myofibers in both appendicular and axial muscles. Defective migration of muscle progenitor cells and impaired proliferation of secondary myoblasts were proven to be responsible for the skeletal muscle dysplasia of mutant mice. Overall, our study shows MET to be a causative gene of arthrogryposis and MET mutation could cause skeletal muscle dysplasia in human beings. John Wiley and Sons Inc. 2019-02-18 2019-03 /pmc/articles/PMC6404111/ /pubmed/30777867 http://dx.doi.org/10.15252/emmm.201809709 Text en © 2019 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Report
Zhou, Hang
Lian, Chengjie
Wang, Tingting
Yang, Xiaoming
Xu, Caixia
Su, Deying
Zheng, Shuhui
Huang, Xiangyu
Liao, Zhiheng
Zhou, Taifeng
Qiu, Xianjian
Chen, Yuyu
Gao, Bo
Li, Yongyong
Wang, Xudong
You, Guoling
Fu, Qihua
Gurnett, Christina
Huang, Dongsheng
Su, Peiqiang
MET mutation causes muscular dysplasia and arthrogryposis
title MET mutation causes muscular dysplasia and arthrogryposis
title_full MET mutation causes muscular dysplasia and arthrogryposis
title_fullStr MET mutation causes muscular dysplasia and arthrogryposis
title_full_unstemmed MET mutation causes muscular dysplasia and arthrogryposis
title_short MET mutation causes muscular dysplasia and arthrogryposis
title_sort met mutation causes muscular dysplasia and arthrogryposis
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404111/
https://www.ncbi.nlm.nih.gov/pubmed/30777867
http://dx.doi.org/10.15252/emmm.201809709
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