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Moshe Frydman, MD; Sarah Vreugde, MD; Ben I. Nageris, MD; Sigal Weiss, MSc; Oz Vahava, MSc; Karen B. Avraham, PhD

Arch Otolaryngol Head Neck Surg. 2000;126:633-637.

Objectives  To describe the detailed auditory phenotype of DFNA15, genetic hearing loss associated with a mutation in the POU4F3 transcription factor, and to define genotype-phenotype correlations, namely, how specific mutations lead to particular clinical consequences.

Design  An analysis of clinical features of hearing-impaired members of an Israeli family, family H, with autosomal dominant–inherited hearing loss.

Setting  Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Audiology, Rabin Medical Center, Petah Tiqwa, Israel; and audiological centers.

Participants  Clinical features of 11 affected and 5 unaffected individuals older than 40 years from family H were studied. Mutation analysis was performed in 6 presymptomatic individuals younger than 30 years; clinical features were analyzed in 4 of these family H members.

Interventions  Hearing was measured by pure-tone audiometry and speech audiometry on all participating relatives of family H. Immittance testing (tympanometry and acoustic reflexes), auditory brainstem response, and otoacoustic emissions were done in a selected patient population.

Results  The patients presented with progressive high-tone sensorineural hearing impairment, which became apparent between ages 18 and 30 years. The hearing impairment became more severe with time, eventually causing significant hearing loss across the spectrum at all frequencies.

Conclusions  Our results indicate that POU4F3 mutation-associated deafness cannot be identified through clinical evaluation, but only through molecular analysis. Intrafamilial variability suggests that other genetic or environmental factors may modify the age at onset and rate of progression.

From the Genetics Institute, Haim Sheba Medical Center, Tel Hashomer, Israel (Dr Frydman); Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (Drs Frydman, Vreugde, and Avraham and Messrs Weiss and Vahava); Departments of Otolaryngology–Head and Neck Surgery and Audiology, Rabin Medical Center, Petah Tiqwa, Israel (Dr Nageris). Mr Vahava is now with Intelligene, Ltd, Jerusalem, Israel. Drs Frydman and Vreugde contributed equally to this report.

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