Progressive sensorineural hearing loss and normal vestibular function in a Dutch DFNB7/11 family with a novel mutation in TMC1.
In a Dutch family with autosomal recessive hearing loss, genome-wide single-nucleotide polymorphism analysis mapped the genetic defect to the DFNB7/11 locus. A novel homozygous A-to-G change in the TMC1 gene was detected near the splice donor site of intron 19 (c.1763+3A→G) segregating with the hearing loss in this family. One of the 6 transmembrane domains and the actual TMC channel domain are predicted to be absent in the mutant protein. The sensorineural hearing impairment in this DFNB7/11 family has a postlingual onset. Audiometric analysis initially showed a steeply downward-sloping threshold configuration. The progressive phenotype in this family resembles the phenotype previously described for families with dominant TMC1 mutations (DFNA36) rather than that of families with recessive TMC1 mutations (DFNB7/11) which invariably cause severe-to-profound prelingual hearing impairment.
Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Anne-Martine R
AM
de Heer
Rob W J
RW
Collin
Patrick L M
PL
Huygen
Margit
M
Schraders
Jaap
J
Oostrik
Myrthe
M
Rouwette
Henricus P M
HP
Kunst
Hannie
H
Kremer
Cor W R J
CW
Cremers
D001309:Auditory Threshold; D001483:Base Sequence; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D022821:RNA Splice Sites / Q000235:genetics; D012720:Severity of Illness Index; D015837:Vestibular Diseases / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*
D008565:Membrane Proteins; D022821:RNA Splice Sites; C451751:TMC1 protein, human