Additional Heterozygous 2507A>C Mutation of WFS1 in Progressive Hearing Loss at Lower Frequencies

Objectives/Hypothesis: To describe the audiological profiles in a Japanese family with autosomal dominant hereditary sensorineural hearing loss (SNHL) and to identify the causative gene. Study Design: A family study at an academic tertiary referral center. Methods: A family with autosomal dominant hereditary SNHL was enrolled. Hearing loss (HL) of affected members showed mid-frequency SNHL in childhood and progressed at lower frequencies with age, resulting in low-frequency SNHL. To understand the pathology of HL of this family, we performed a genetic analysis of WFS1, TECTA, and GJB2 by direct sequencing, and further audiovestibular examinations, including speech audiometry, distortion product otoacoustic emissions, electrocochleography, auditory brainstem responses, and electronystagniography for some affected members. Results: A heterozygous A-to-C nucleotide transversion (c.2507A>C), resulting in a lysine-to-threonine substitution at codon 836 (K836T) was identified in exon 8 of WFS1. K836T was segregated with HL in the 15 participants in the genetic study but was not detected in the 212 normal chromosomes. Only polymorphic changes were detected in TECTA and GJB2. Audiovestibular examinations indicated purely cochlear HL and normal vestibular function. The summating potential/action potential ratios in electrocochleography increased in the bilateral ears of the proband. Conclusions: The family described with autosomal dominant inheritance of K836T of the WFS1 gene demonstrates a progressive hearing loss in the lower frequencies.