[PROVISIONAL] Whole exome sequencing identifies a novel variant in an apoptosis-inducing factor gene associated with X-linked recessive hearing loss in a Chinese Family

Abstract We report on the genetic analysis of a Chinese family in which four male patients presented with postlingual progressive hearing loss, associated with distal muscle wasting and unsteady ataxic gait. Using whole exome sequencing, we identified a new pathogenic variant (c.1463C>T, p.Pro488...

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Main Authors: Qi Wang, Xingxing Lu, Zhiwei Ding, Yu Qi, Yuhe Liu
Format: Article
Language:English
Published: Sociedade Brasileira de Genética
Series:Genetics and Molecular Biology
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572019005021101&lng=en&tlng=en
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author Qi Wang
Xingxing Lu
Zhiwei Ding
Yu Qi
Yuhe Liu
author_facet Qi Wang
Xingxing Lu
Zhiwei Ding
Yu Qi
Yuhe Liu
author_sort Qi Wang
collection DOAJ
description Abstract We report on the genetic analysis of a Chinese family in which four male patients presented with postlingual progressive hearing loss, associated with distal muscle wasting and unsteady ataxic gait. Using whole exome sequencing, we identified a new pathogenic variant (c.1463C>T, p.Pro488Leu) in AIFM1 gene, which encodes the apoptosis-inducing factor mitochondrion-associated 1 precursor. AIFM1 gene is involved in the mitochondrial respiratory chain and cellular caspase-independent apoptosis pathway and has been reported to cause multiple phenotypes including hearing loss. The p.Pro488Leu missense variant segregated with symptoms in the pedigree, and was not found in the dbSNP database, databases of genomes and SNP in the Chinese population, in 74 patients with sporadic hearing loss, or in 108 normal individuals. We also verified that this variant AIFM1 in 293T cells enhanced cell apoptosis rates compared with 293T cells transfected with wild-type AIFM1. Different variations of AIFM1 gene give rise to different phenotypes in patients, and this is the second reported family with a variant in the C-terminal domain of AIFM1 showing the phenotype of hearing loss and peripheral neuropathy.
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spelling doaj.art-e2e9b8f3184c4edd8188f12b725cca8a2022-12-22T00:03:22ZengSociedade Brasileira de GenéticaGenetics and Molecular Biology1678-4685010.1590/1678-4685-gmb-2018-0051S1415-47572019005021101[PROVISIONAL] Whole exome sequencing identifies a novel variant in an apoptosis-inducing factor gene associated with X-linked recessive hearing loss in a Chinese FamilyQi WangXingxing LuZhiwei DingYu QiYuhe LiuAbstract We report on the genetic analysis of a Chinese family in which four male patients presented with postlingual progressive hearing loss, associated with distal muscle wasting and unsteady ataxic gait. Using whole exome sequencing, we identified a new pathogenic variant (c.1463C>T, p.Pro488Leu) in AIFM1 gene, which encodes the apoptosis-inducing factor mitochondrion-associated 1 precursor. AIFM1 gene is involved in the mitochondrial respiratory chain and cellular caspase-independent apoptosis pathway and has been reported to cause multiple phenotypes including hearing loss. The p.Pro488Leu missense variant segregated with symptoms in the pedigree, and was not found in the dbSNP database, databases of genomes and SNP in the Chinese population, in 74 patients with sporadic hearing loss, or in 108 normal individuals. We also verified that this variant AIFM1 in 293T cells enhanced cell apoptosis rates compared with 293T cells transfected with wild-type AIFM1. Different variations of AIFM1 gene give rise to different phenotypes in patients, and this is the second reported family with a variant in the C-terminal domain of AIFM1 showing the phenotype of hearing loss and peripheral neuropathy.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572019005021101&lng=en&tlng=enwhole exome sequencingapoptosis-inducing factorAIFM1X-linked recessive hereditary hearing loss
spellingShingle Qi Wang
Xingxing Lu
Zhiwei Ding
Yu Qi
Yuhe Liu
[PROVISIONAL] Whole exome sequencing identifies a novel variant in an apoptosis-inducing factor gene associated with X-linked recessive hearing loss in a Chinese Family
Genetics and Molecular Biology
whole exome sequencing
apoptosis-inducing factor
AIFM1
X-linked recessive hereditary hearing loss
title [PROVISIONAL] Whole exome sequencing identifies a novel variant in an apoptosis-inducing factor gene associated with X-linked recessive hearing loss in a Chinese Family
title_full [PROVISIONAL] Whole exome sequencing identifies a novel variant in an apoptosis-inducing factor gene associated with X-linked recessive hearing loss in a Chinese Family
title_fullStr [PROVISIONAL] Whole exome sequencing identifies a novel variant in an apoptosis-inducing factor gene associated with X-linked recessive hearing loss in a Chinese Family
title_full_unstemmed [PROVISIONAL] Whole exome sequencing identifies a novel variant in an apoptosis-inducing factor gene associated with X-linked recessive hearing loss in a Chinese Family
title_short [PROVISIONAL] Whole exome sequencing identifies a novel variant in an apoptosis-inducing factor gene associated with X-linked recessive hearing loss in a Chinese Family
title_sort provisional whole exome sequencing identifies a novel variant in an apoptosis inducing factor gene associated with x linked recessive hearing loss in a chinese family
topic whole exome sequencing
apoptosis-inducing factor
AIFM1
X-linked recessive hereditary hearing loss
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572019005021101&lng=en&tlng=en
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