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 electronystagmography 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.
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 electronystagmography 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.
Authors: Nanna D Rendtorff; Marianne Lodahl; Houda Boulahbel; Ida R Johansen; Arti Pandya; Katherine O Welch; Virginia W Norris; Kathleen S Arnos; Maria Bitner-Glindzicz; Sarah B Emery; Marilyn B Mets; Toril Fagerheim; Kristina Eriksson; Lars Hansen; Helene Bruhn; Claes Möller; Sture Lindholm; Stefan Ensgaard; Marci M Lesperance; Lisbeth Tranebjaerg Journal: Am J Med Genet A Date: 2011-04-28 Impact factor: 2.802