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

Standard

A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families. / Newman, William; Demain, Leigh; O'Keefe, Raymond; Molina Ramirez, Leslie.

In: Journal of Human Genetics, 12.12.2019.

Research output: Contribution to journalArticlepeer-review

Harvard

APA

Vancouver

Author

Bibtex

@article{4b53b81214f34132bdf50e8549887717,
title = "A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families.",
abstract = "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.",
keywords = "Perrault syndrome, hearing loss, ovarian insufficiency, rare disease, genetics, Mitochondria",
author = "William Newman and Leigh Demain and Raymond O'Keefe and {Molina Ramirez}, Leslie",
year = "2019",
month = dec,
day = "12",
doi = "10.1038/s10038-019-0706-1",
language = "English",
journal = "Journal of Human Genetics",
issn = "1434-5161",
publisher = "Springer Nature",

}

RIS

TY - JOUR

T1 - A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families.

AU - Newman, William

AU - Demain, Leigh

AU - O'Keefe, Raymond

AU - Molina Ramirez, Leslie

PY - 2019/12/12

Y1 - 2019/12/12

N2 - 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.

AB - 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.

KW - Perrault syndrome

KW - hearing loss

KW - ovarian insufficiency

KW - rare disease

KW - genetics

KW - Mitochondria

U2 - 10.1038/s10038-019-0706-1

DO - 10.1038/s10038-019-0706-1

M3 - Article

JO - Journal of Human Genetics

JF - Journal of Human Genetics

SN - 1434-5161

ER -