Nature Genetics
20, 194 - 197 (1998)
doi:10.1038/2503
Nonsyndromic hearing impairment is associated with a mutation in
DFNA5Lut Van Laer1, Egbert H. Huizing2, Margriet Verstreken1, 3, Diederick van Zuijlen2, Jan G. Wauters1, Paul J. Bossuyt1, Paul Van de Heyning3, Wyman T. McGuirt4, Richard J.H. Smith4, Patrick J. Willems1, P. Kevin Legan5, Guy P. Richardson5
& Guy Van Camp11
Department of Medical Genetics, University of Antwerp
(UIA), Universiteitsplein 1, 2610
Antwerp, Belgium. 2
Department of Otorhinolaryngology, University Hospital
of Utrecht, Heidelberglaan 100, 3584
CX Utrecht, The Netherlands. 3
Department of Otorhinolaryngology, University of Antwerp
(UIA), Universiteitsplein 1, 2610
Antwerp, Belgium. 4
Department of Otolaryngology, University of Iowa Hospitals
and Clinics, 650 Newton Road, E230 GH Iowa City
, Iowa 52242, USA.
5
School of Biological Sciences, University of Sussex,
Falmer,
Brighton, BN1 9QG, UK.
Correspondence should be addressed to Guy Van Camp gvcamp@uia.ua.ac.beNonsyndromic hearing impairment is one of the most heterogeneous hereditary
conditions, with more than 40 loci mapped on the human genome1,
however, only a limited number of genes implicated in hearing loss have been
identified. We previously reported linkage to chromosome 7p15 for autosomal
dominant hearing impairment segregating in an extended Dutch family2,
3
(DFNA5). Here, we report a further refinement of the DFNA5 candidate
region and the isolation of a gene from this region that is expressed in the
cochlea. In intron 7 of this gene, we identified an insertion/deletion mutation
that does not affect intron-exon boundaries, but deletes five G-triplets at
the 3' end of the intron. The mutation co-segregated with deafness in the
family and causes skipping of exon 8, resulting in premature termination of
the open reading frame. As no physiological function could be assigned, the
gene was designated DFNA5.
|
