Whole-exome sequencing identifies a novel missense variant within LOXHD1 causing rare hearing loss in a Chinese family

• Main Authors: Na Shen (Author), Ting Wang (Author), Delei Li (Author), Aiguo Liu (Author), Yanjun Lu (Author)
• Format: Book
• Published: BMC, 2019-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/s12881-019-0758-2; 1471-2350
• Keywords: Deafness, autosomal recessive 77 (DFNB77); Non-syndromic hearing loss (NSHL); Lipoxygenase homology domains 1 (LOXHD1); Genetic variant; Whole-exome sequencing (WES); Internal medicine; RC31-1245; Genetics; QH426-470
• Source: BMC Medical Genetics, Vol 20, Iss 1, Pp 1-6 (2019)

Abstract Background Deafness, autosomal recessive 77 (DFNB77) is a rare non-syndromic hearing loss (NSHL) worldwide, which is caused by deleterious variants within lipoxygenase homology domains 1 (LOXHD1). Here we identified that a novel missense variant of LOXHD1 was associated with NSHL in a Chinese family under consanguineous marriage. Case presentation A 28-year-old woman suffered a bilateral profound NSHL. Impedance audiometry, temporal bone computerized tomography (TBCT) scans and magnetic resonance imaging-inner ear hydrography (MRI-IEH) did not find any obvious abnormality of middle or inner ear. Routine genetic detection did not find pathogenic variants in common HL-associated genes. Therefore, we performed a whole-exome sequencing (WES) in this family. By trio-WES, co-segregation validation and bioinformatics analysis, we revealed that a novel homozygous variant in this patient, LOXHD1: c.5948C > T (p.S1983F), might be the pathogenic factor. Her parents (heterozygotes) and brother (wild-type) were asymptomatic. Conclusions We successfully identified a novel variant of LOXHD1 associated with a rare NSHL from a Chinese family. Our finds highlight the effectiveness of trio-WES for molecular diagnosis of rare NHSL, and expand the genotypic spectrum of DFNB77.