WFS1 and GJB2 mutations in patients with bilateral low-frequency sensorineural hearing loss

Evaluating the prevalence of specific gene mutations associated with a certain audiometric configuration facilitates clinical assessment of patients with sensorineural hearing loss (SNHL). WFS1 is responsible for autosomal dominant nonsyndromic deafness 6/14/38 and is the most frequent genetic cause of low-frequency SNHL (LFSNHL); however, the exact prevalence of WFS1 mutations in LFSNHL is unknown. Therefore, we evaluated genetic mutations and clinical features in patients with nonsyndromic bilateral LFSNHL, focusing on the WFS1.Retrospective case series from 2002 to 2013 at the National Hospital Organization Tokyo Medical Center and collaborating hospitals.WFS1, GJB2, and mitochondrial DNA mutation screening was carried out for 74 of 1,007 Japanese probands with bilateral LFSNHL.WFS1 and GJB2 mutations were identified in eight of 74 cases (10.8%). Four cases had heterozygous WFS1 mutations; one case had a heterozygous WFS1 mutation and a heterozygous GJB2 mutation; and three cases had biallelic GJB2 mutations. Three cases with WFS1 mutations were sporadic; two of them were confirmed to be caused by a de novo mutation based on the genetic analysis of their parents. In the case with mutations in both WFS1 and GJB2, a de novo mutation of WFS1 was confirmed in the proband's mother by genetic screening of the mother's parents.Genetic screening focusing on LFSNHL has not been conducted. The present study first revealed the prevalence of specific gene mutations. WFS1 autosomal dominant mutations were identified even in sporadic cases. Our results also suggested a mutational hotspot in WFS1.4. Laryngoscope, 127:E324-E329, 2017.