Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783400800452608000 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6404111 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zhouhang metmutationcausesmusculardysplasiaandarthrogryposis AT lianchengjie metmutationcausesmusculardysplasiaandarthrogryposis AT wangtingting metmutationcausesmusculardysplasiaandarthrogryposis AT yangxiaoming metmutationcausesmusculardysplasiaandarthrogryposis AT xucaixia metmutationcausesmusculardysplasiaandarthrogryposis AT sudeying metmutationcausesmusculardysplasiaandarthrogryposis AT zhengshuhui metmutationcausesmusculardysplasiaandarthrogryposis AT huangxiangyu metmutationcausesmusculardysplasiaandarthrogryposis AT liaozhiheng metmutationcausesmusculardysplasiaandarthrogryposis AT zhoutaifeng metmutationcausesmusculardysplasiaandarthrogryposis AT qiuxianjian metmutationcausesmusculardysplasiaandarthrogryposis AT chenyuyu metmutationcausesmusculardysplasiaandarthrogryposis AT gaobo metmutationcausesmusculardysplasiaandarthrogryposis AT liyongyong metmutationcausesmusculardysplasiaandarthrogryposis AT wangxudong metmutationcausesmusculardysplasiaandarthrogryposis AT youguoling metmutationcausesmusculardysplasiaandarthrogryposis AT fuqihua metmutationcausesmusculardysplasiaandarthrogryposis AT gurnettchristina metmutationcausesmusculardysplasiaandarthrogryposis AT huangdongsheng metmutationcausesmusculardysplasiaandarthrogryposis AT supeiqiang metmutationcausesmusculardysplasiaandarthrogryposis |