Clinical characterization of genetic hearing loss caused by a mutation in the POU4F3 transcription factor.
OBJECTIVE
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.


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


METHODS
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.


METHODS
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.


METHODS
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.
Frydman
M
M
Genetics Institute, Haim Sheba Medical Center, Tel Hashomer, Israel.
Vreugde
S
S
Nageris
B I
BI
Weiss
S
S
Vahava
O
O
Avraham
K B
KB
D000328:Adult; D001301:Audiometry, Pure-Tone; D002869:Chromosome Aberrations / Q000235:genetics*; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D006580:Genetic Carrier Screening; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007557:Israel; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors / Q000235:genetics*
D018398:Homeodomain Proteins; C111223:POU4F3 protein, human; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors