A novel pathogenic variant in OSBPL2 linked to hereditary late-onset deafness in a Mongolian family

Abstract

BackgroundTo investigate the clinical features and the underlying causal gene of a family with hereditary late-onset deafness in Inner Mongolia of China, and to provide evidence for the early genetic screening and diagnosis of this disease.MethodsFamily data were collected to draw a pedigree. Audiological testing and physical examination of the family members were conducted following questionnaire. Genomic DNA was extracted from peripheral blood of 5 family members (3 patients and 2 normal control) and subjected to whole genome sequencing for identifying deafness casual genes. The pathogenic variant in the deafness gene was further confirmed by Sanger sequencing.ResultsThe family is composed of a total of 6 generations, with 53 traceable individuals. In this family,19 of them were diagnosed with post lingual deafness with the age of onset between 10 and 40 years, displaying delayed and progressive hearing loss. Patients with hearing loss showed bilateral symmetry and mild to severe sensorineural deafness. The pattern of deafness inheritance in this family is autosomal dominant. Whole genome sequencing identified a novel pathogenic frameshift mutation, c.158_159delAA (p.Gln53Arg fs*100) in the gene OSBPL2 (Oxysterol-binding protein-related protein 2, NM_144498.2), which is absent from genomic data of 201 unrelated normal subjects. This pathogenic variant was further validated by Sanger sequencing, and was found to co-segregate in this family.ConclusionsWhole genome sequencing identified a two-nucleotide deletion in OSBPL2 (c.158_159delAA) as the pathogenic variant for deafness in the family. Our finding expands the mutational spectrum of OSBPL2 and contributes to the pathogenic variant list in genetic counseling for deafness screening.Electronic supplementary materialThe online version of this article (10.1186/s12881-019-0781-3) contains supplementary material, which is available to authorized users.

Oxysterol-binding protein-like 2 contributes to the developmental progression of preadipocytes by binding to β-catenin

“…In the previous study, we described the association of OSBPL2 mutations with autosomal dominant nonsyndromic hearing loss in a large affected Chinese family 50 , which were then verified in other affected families. 51 , 52 . To confirm the effect of OSBPL2 disruption on hearing loss, we established OSBPL2 -disrupted Bama mini pig models.…”

Searching for the Molecular Basis of Partial Deafness

“…This variant truncates the protein and is not recorded in population databases. In 2019, it was identified as causative for HL in a Mongolian family [ 14 ] and included in the HGMD database (CD193739).…”

OSBPL2 Is Required for the Binding of COPB1 to ATGL and the Regulation of Lipid Droplet Lipolysis

“…Our laboratory and others had previously identified that OSBPL2 was associated with autosomal dominant nonsyndromic hearing loss (Thoenes et al, 2015;Wu et al, 2019;Xing et al, 2015). To confirm the consistent effect of OSBPL2/ORP2 in hearing loss by both genotype and phenotype, we successfully simulated human hearing loss phenotypes in both Bama mini pig and zebrafish models.…”