Novel HARS2 missense variants identified in individuals with sensorineural hearing impairment and Perrault syndrome.

• 影响指数: 2.465
• 发表时间: Mar 2020
• 来源期刊: Eur J Med Genet
• DOI: 10.1016/j.ejmg.2019.103733
• PMID: 31449985
• 文章类型: Case Reports
• 中科院分区: Q3
• 方向: 生物
• 作者列表: Karstensen HG,Rendtorff ND,Hindbæk LS,Colombo R,Stein A,Birkebæk NH,Hartmann-Petersen R,Lindorff-Larsen K,Højland AT,Petersen MB,Tranebjærg L

关键词: HARS2; Next-generation sequencing; Perrault syndrome; Premature ovarian insufficiency; Sensorineural hearing impairment

Mesh: Adolescent; Adult; Amino Acyl-tRNA Synthetases / genetics; Child; Female; Gonadal Dysgenesis, 46,XX / genetics physiopathology; Hearing Loss / genetics physiopathology; Hearing Loss, Sensorineural / genetics physiopathology; Heterozygote; High-Throughput Nucleotide Sequencing; Humans; Male; Mutation, Missense; Pedigree; Primary Ovarian Insufficiency / genetics; Whole Exome Sequencing

Abstract

Biallelic variants in HARS2 have been associated with Perrault syndrome, characterized by sensorineural hearing impairment and premature ovarian insufficiency. Here we report three novel families, compound heterozygous for missense variants in HARS2 identified by next-generation sequencing, namely c.172A > G (p.Lys58Glu) and c.448C > T (p.Arg150Cys) identified in two sisters aged 13 and 16 years and their older brother, c.448C > T (p.Arg150Cys) and c.980G > A (p.Arg327Gln) identified in a seven year old girl, and finally c.137T > A (p.Leu46Gln) and c.259C > T (p.Arg87Cys) identified in a 32 year old woman. Clinically, all five individuals presented with early onset, rapidly progressive hearing impairment. Whereas the oldest female fulfilled the criteria of Perrault syndrome, the three younger females, aged 7, 13 and 16, all had apparently normal ovarian function, apart from irregular menstrual periods in the oldest female at age 16. The present report expands the list of HARS2 variants and helps gain further knowledge to the phenotype.