A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families.,Journal of Human Genetics

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A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families.
Journal of Human Genetics ( IF 2.6 ) Pub Date : 2019-12-12 , DOI: 10.1038/s10038-019-0706-1
Leigh A M Demain _{1,

2} , Erica H Gerkes ₃ , Richard J H Smith ₄ , Leslie P Molina-Ramirez _{1,

2} , Raymond T O'Keefe ₁ , William G Newman _{1,

2}

Affiliation

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.

中文翻译：

HARS2 中反复出现的错义变异会导致三个不相关的家庭出现不同程度的感音神经性听力损失。

HARS2 编码线粒体组氨酰-tRNA 合成酶 (HARS2)，它将组氨酸与其在线粒体基质中的同源 tRNA 连接起来。 HARS2 中的双等位基因变异与 Perrault 综合征相关，Perrault 综合征是一种罕见的隐性病症，其特征是两性的感音神经性听力损失和 46,XX 女性的原发性卵巢功能不全。一些佩罗综合征患者具有更广泛的表型谱和神经系统特征，包括共济失调和周围神经病变。在这里，我们报告了与感音神经性听力损失相关的 HARS2 复发性变异。在来自三个不相关家族的受影响个体中，变异 HARS2 c.1439G>A p.(Arg480His) 作为杂合变异反式存在于假定的致病变异中。等位基因 HARS2 c.1439G>A p.(Arg480His) 在一般人群中的患病率较低，并且在三个听力损失家庭中存在，证实了该变异的致病性，并说明了 Perrault 综合征在男性中表现为非综合征性听力损失以及青春期前的女性。

更新日期：2019-12-13

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