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Indentification of novel MSTO1 compound heterozygous mutations in a Chinese family with recessive cerebellar atrophy and ataxia

Misato mitochondrial distribution and morphology regulator 1 (MSTO1) is a nuclear-encoded cytoplasmic protein involved in mitochondrial fusion and distribution. Its disruption causes an extremely rare mitochondrial disorder characterized by early-onset myopathy and cerebellar ataxia. The genotype-ph...

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Autores principales: Chen, Jia, Xiao, Junfang, Chen, Ge, Xu, Qiang, Wu, Xingwu, Tian, Lifeng, Huang, Zhihui, Xin, Cailin, Zhao, Yan, Guo, Zhen, Zou, Yang, Wu, Qiongfang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9712729/
https://www.ncbi.nlm.nih.gov/pubmed/36468072
http://dx.doi.org/10.3389/fneur.2022.988519
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author Chen, Jia
Xiao, Junfang
Chen, Ge
Xu, Qiang
Wu, Xingwu
Tian, Lifeng
Huang, Zhihui
Xin, Cailin
Zhao, Yan
Guo, Zhen
Zou, Yang
Wu, Qiongfang
author_facet Chen, Jia
Xiao, Junfang
Chen, Ge
Xu, Qiang
Wu, Xingwu
Tian, Lifeng
Huang, Zhihui
Xin, Cailin
Zhao, Yan
Guo, Zhen
Zou, Yang
Wu, Qiongfang
author_sort Chen, Jia
collection PubMed
description Misato mitochondrial distribution and morphology regulator 1 (MSTO1) is a nuclear-encoded cytoplasmic protein involved in mitochondrial fusion and distribution. Its disruption causes an extremely rare mitochondrial disorder characterized by early-onset myopathy and cerebellar ataxia. The genotype-phenotype correlation in the MSTO1 gene is rarely studied before 2017, and only 25 mutations have been described in the patients. Here, we reported two siblings with progressive cerebellar atrophy and ataxia in a Chinese family. Two compound heterozygous mutations in the MSTO1 gene, a novel missense mutation c.571C>T (p.Arg191Trp), and a reported frameshift mutation c.1259delG (p.Gly420ValfsTer2) were identified in the patients by whole exome sequencing. in vitro experiments found both of the mutations lead to reduced protein abundance and link to decreased mtDNA content. Except for ataxia and delayed motor, both of the siblings also have low birth weights, learning difficulties, and dysarthria. Our report enriched the genotype and phenotype spectrums of the MSTO1-related disorder and supported the recessive inheritance of the disease.
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spelling pubmed-97127292022-12-02 Indentification of novel MSTO1 compound heterozygous mutations in a Chinese family with recessive cerebellar atrophy and ataxia Chen, Jia Xiao, Junfang Chen, Ge Xu, Qiang Wu, Xingwu Tian, Lifeng Huang, Zhihui Xin, Cailin Zhao, Yan Guo, Zhen Zou, Yang Wu, Qiongfang Front Neurol Neurology Misato mitochondrial distribution and morphology regulator 1 (MSTO1) is a nuclear-encoded cytoplasmic protein involved in mitochondrial fusion and distribution. Its disruption causes an extremely rare mitochondrial disorder characterized by early-onset myopathy and cerebellar ataxia. The genotype-phenotype correlation in the MSTO1 gene is rarely studied before 2017, and only 25 mutations have been described in the patients. Here, we reported two siblings with progressive cerebellar atrophy and ataxia in a Chinese family. Two compound heterozygous mutations in the MSTO1 gene, a novel missense mutation c.571C>T (p.Arg191Trp), and a reported frameshift mutation c.1259delG (p.Gly420ValfsTer2) were identified in the patients by whole exome sequencing. in vitro experiments found both of the mutations lead to reduced protein abundance and link to decreased mtDNA content. Except for ataxia and delayed motor, both of the siblings also have low birth weights, learning difficulties, and dysarthria. Our report enriched the genotype and phenotype spectrums of the MSTO1-related disorder and supported the recessive inheritance of the disease. Frontiers Media S.A. 2022-11-17 /pmc/articles/PMC9712729/ /pubmed/36468072 http://dx.doi.org/10.3389/fneur.2022.988519 Text en Copyright © 2022 Chen, Xiao, Chen, Xu, Wu, Tian, Huang, Xin, Zhao, Guo, Zou and Wu. 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 Neurology
Chen, Jia
Xiao, Junfang
Chen, Ge
Xu, Qiang
Wu, Xingwu
Tian, Lifeng
Huang, Zhihui
Xin, Cailin
Zhao, Yan
Guo, Zhen
Zou, Yang
Wu, Qiongfang
Indentification of novel MSTO1 compound heterozygous mutations in a Chinese family with recessive cerebellar atrophy and ataxia
title Indentification of novel MSTO1 compound heterozygous mutations in a Chinese family with recessive cerebellar atrophy and ataxia
title_full Indentification of novel MSTO1 compound heterozygous mutations in a Chinese family with recessive cerebellar atrophy and ataxia
title_fullStr Indentification of novel MSTO1 compound heterozygous mutations in a Chinese family with recessive cerebellar atrophy and ataxia
title_full_unstemmed Indentification of novel MSTO1 compound heterozygous mutations in a Chinese family with recessive cerebellar atrophy and ataxia
title_short Indentification of novel MSTO1 compound heterozygous mutations in a Chinese family with recessive cerebellar atrophy and ataxia
title_sort indentification of novel msto1 compound heterozygous mutations in a chinese family with recessive cerebellar atrophy and ataxia
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9712729/
https://www.ncbi.nlm.nih.gov/pubmed/36468072
http://dx.doi.org/10.3389/fneur.2022.988519
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