OBJECTIVE: To characterize the auditory and vestibular phenotype of autosomal dominant nonsyndromic DFNA36 hearing loss. STUDY DESIGN: Clinical evaluation of individuals with DFNA36 hearing loss linked to the D572N mutation of transmembrane channel-like gene 1 (TMC1). Medical history interviews, physical examinations, and pure-tone air conduction audiometry were performed in the field. Audiology and radiology reports were available and retrospectively reviewed for a subset of subjects. SETTING: Primary, secondary, and tertiary referral centers (retrospectively reviewed studies); subjects' homes (prospective clinical evaluations). PATIENTS: Thirteen affected members of a North American Caucasian family segregating DFNA36 hearing loss. MAIN OUTCOME MEASURES: Pure-tone audiometric thresholds and their rates of progression. RESULTS: Subjects had bilateral, symmetric, sensorineural hearing loss with a postlingual onset in the first decade of life. High frequencies were initially affected, followed by rapid progression (5.9 dB/yr for the 0.5/1/2/4-kHz pure-tone average) to profound deafness across all frequencies by the second decade of life. Two individuals had excellent auditory-verbal communication after rehabilitation with cochlear implants placed over two decades after total deafening. CONCLUSIONS: DFNA36 has one of the earliest onsets and most rapid rates of progression among the autosomal dominant non-syndromic hearing loss phenotypes. These distinctive features should facilitate its clinical detection and the development of clinical-molecular genetic diagnostic algorithms for dominant nonsyndromic hearing loss.
OBJECTIVE: To characterize the auditory and vestibular phenotype of autosomal dominant nonsyndromic DFNA36 hearing loss. STUDY DESIGN: Clinical evaluation of individuals with DFNA36hearing loss linked to the D572N mutation of transmembrane channel-like gene 1 (TMC1). Medical history interviews, physical examinations, and pure-tone air conduction audiometry were performed in the field. Audiology and radiology reports were available and retrospectively reviewed for a subset of subjects. SETTING: Primary, secondary, and tertiary referral centers (retrospectively reviewed studies); subjects' homes (prospective clinical evaluations). PATIENTS: Thirteen affected members of a North American Caucasian family segregating DFNA36hearing loss. MAIN OUTCOME MEASURES: Pure-tone audiometric thresholds and their rates of progression. RESULTS: Subjects had bilateral, symmetric, sensorineural hearing loss with a postlingual onset in the first decade of life. High frequencies were initially affected, followed by rapid progression (5.9 dB/yr for the 0.5/1/2/4-kHz pure-tone average) to profound deafness across all frequencies by the second decade of life. Two individuals had excellent auditory-verbal communication after rehabilitation with cochlear implants placed over two decades after total deafening. CONCLUSIONS:DFNA36 has one of the earliest onsets and most rapid rates of progression among the autosomal dominant non-syndromic hearing loss phenotypes. These distinctive features should facilitate its clinical detection and the development of clinical-molecular genetic diagnostic algorithms for dominant nonsyndromic hearing loss.
Authors: Robert W Eppsteiner; A Eliot Shearer; Michael S Hildebrand; Adam P Deluca; Haihong Ji; Camille C Dunn; Elizabeth A Black-Ziegelbein; Thomas L Casavant; Terry A Braun; Todd E Scheetz; Steven E Scherer; Marlan R Hansen; Bruce J Gantz; Richard J H Smith Journal: Hear Res Date: 2012-08-28 Impact factor: 3.208
Authors: Yoshiyuki Kawashima; Gwenaëlle S G Géléoc; Kiyoto Kurima; Valentina Labay; Andrea Lelli; Yukako Asai; Tomoko Makishima; Doris K Wu; Charles C Della Santina; Jeffrey R Holt; Andrew J Griffith Journal: J Clin Invest Date: 2011-11-21 Impact factor: 14.808
Authors: Nele Hilgert; Kelly Monahan; Kiyoto Kurima; Cindy Li; Rick A Friedman; Andrew J Griffith; Guy Van Camp Journal: J Hum Genet Date: 2009-01-30 Impact factor: 3.172