Purchase this article with an account.
Shuhei Kameya, Daiki Kubota, Sachiko Kikuchi, Kiyoko Gocho, Keiichiro Akeo, Kunihiko Yamaki, Hiroshi Takahashi; Whole exome sequencing reveals DFNB31 mutations associated with mild cone-rod dystrophy and sensorineural hearing loss in Japanese family.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3230.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To identify the genetic defect of a non-consanguineous Japanese family with mild cone-rod dystrophy and sensorineural hearing loss using whole exome sequencing (WES).
Detailed ophthalmic and auditory examinations including high-resolution adaptive optics (AO) fundus imaging were performed on the proband and her family member. Whole exome sequencing (WES) was applied to the DNA obtained from the proband. Filtering with available genomic databases and in silico analyses were used to identify the disease causing variants. Sanger sequencing and co-segregation analysis of the proband and her family members were performed to identify the most likely pathogenic variant.
Using WES on the DNA sample of the proband, we identified a compound heterozygous variants c.321C>A, p.Asp107Glu and c.668G>A, p.Arg223His in the DFNB31, a gene associated with Usher syndrome. Both of the mutation were predicted as damaging at SIFT prediction program. Minor allele frequency (MAF) of these mutation in ExAC database were 0.003% and 0.67% in worldwide and 0.04% and 2.3% in East Asian respectively. MAF of these mutation in HGVD database were 1.1% and 2.2% in Japanese population. The variants were verified by Sanger sequencing and were co-segregated with the disease in five members of the family. The affected sister of the proband also harbor a compound heterozygous variants. Fundus appearance of both patients were normal, however electrophysiological analysis revealed a mild cone-rod dystrophy phenotype in the proband and her sister. SD-OCT images of both patients showed blurred EZ and IZ. AO imaging revealed reduced cone density around fovea compared to peripheral region in both patients. Auditory examinations of both patients revealed slight sensorineural hearing loss mainly at high frequency.
Our data indicate that mutations of DFNB31 can cause mild cone-rod dystrophy and sensorineural hearing loss in Japanese patients. Although there are several Japanese patients reported to have only hearing loss with DFNB31 mutation, this is the first cases to show DFNB31 mutation in Japanese family harboring both hearing loss and cone-rod dystrophy. Ophthalmological and auditory phenotype of these patients were very mild. Comparatively high MAF of these mutations in Japanese population may related to the findability of retinal and hearing abnormality.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
This PDF is available to Subscribers Only