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A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families

HARS2 encodes mitochondrial histidyl-tRNA synthetase (HARS2), which links histidine to its cognate tRNA in the mitochondrial matrix. Biallelic variants in HARS2 are associated with Perrault syndrome, a rare recessive condition characterized by sensorineural hearing loss in both sexes and primary ova...

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Autores principales: Demain, Leigh A. M., Gerkes, Erica. H., Smith, Richard J. H., Molina-Ramirez, Leslie P., O’Keefe, Raymond T., Newman, William G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500128/
https://www.ncbi.nlm.nih.gov/pubmed/31827252
http://dx.doi.org/10.1038/s10038-019-0706-1
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author Demain, Leigh A. M.
Gerkes, Erica. H.
Smith, Richard J. H.
Molina-Ramirez, Leslie P.
O’Keefe, Raymond T.
Newman, William G.
author_facet Demain, Leigh A. M.
Gerkes, Erica. H.
Smith, Richard J. H.
Molina-Ramirez, Leslie P.
O’Keefe, Raymond T.
Newman, William G.
author_sort Demain, Leigh A. M.
collection PubMed
description HARS2 encodes mitochondrial histidyl-tRNA synthetase (HARS2), which links histidine to its cognate tRNA in the mitochondrial matrix. Biallelic variants in HARS2 are associated with Perrault syndrome, a rare recessive condition characterized by sensorineural hearing loss in both sexes and primary ovarian insufficiency in 46,XX females. Some individuals with Perrault syndrome have a broader phenotypic spectrum with neurological features, including ataxia and peripheral neuropathy. Here, we report a recurrent variant in HARS2 in association with sensorineural hearing loss. In affected individuals from three unrelated families, the variant HARS2 c.1439G>A p.(Arg480His) is present as a heterozygous variant in trans to a putative pathogenic variant. The low prevalence of the allele HARS2 c.1439G>A p.(Arg480His) in the general population and its presence in three families with hearing loss, confirm the pathogenicity of this variant and illustrate the presentation of Perrault syndrome as nonsyndromic hearing loss in males and prepubertal females.
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spelling pubmed-75001282020-09-18 A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families Demain, Leigh A. M. Gerkes, Erica. H. Smith, Richard J. H. Molina-Ramirez, Leslie P. O’Keefe, Raymond T. Newman, William G. J Hum Genet Article HARS2 encodes mitochondrial histidyl-tRNA synthetase (HARS2), which links histidine to its cognate tRNA in the mitochondrial matrix. Biallelic variants in HARS2 are associated with Perrault syndrome, a rare recessive condition characterized by sensorineural hearing loss in both sexes and primary ovarian insufficiency in 46,XX females. Some individuals with Perrault syndrome have a broader phenotypic spectrum with neurological features, including ataxia and peripheral neuropathy. Here, we report a recurrent variant in HARS2 in association with sensorineural hearing loss. In affected individuals from three unrelated families, the variant HARS2 c.1439G>A p.(Arg480His) is present as a heterozygous variant in trans to a putative pathogenic variant. The low prevalence of the allele HARS2 c.1439G>A p.(Arg480His) in the general population and its presence in three families with hearing loss, confirm the pathogenicity of this variant and illustrate the presentation of Perrault syndrome as nonsyndromic hearing loss in males and prepubertal females. Springer Singapore 2019-12-12 2020 /pmc/articles/PMC7500128/ /pubmed/31827252 http://dx.doi.org/10.1038/s10038-019-0706-1 Text en © The Author(s) 2019 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Demain, Leigh A. M.
Gerkes, Erica. H.
Smith, Richard J. H.
Molina-Ramirez, Leslie P.
O’Keefe, Raymond T.
Newman, William G.
A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families
title A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families
title_full A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families
title_fullStr A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families
title_full_unstemmed A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families
title_short A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families
title_sort recurrent missense variant in hars2 results in variable sensorineural hearing loss in three unrelated families
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500128/
https://www.ncbi.nlm.nih.gov/pubmed/31827252
http://dx.doi.org/10.1038/s10038-019-0706-1
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