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Involvement of DFNB59 mutations in autosomal recessive nonsyndromic hearing impairment
Author(s) -
Collin Rob W.J.,
Kalay Ersan,
Oostrik Jaap,
Çaylan Refik,
Wollnik Bernd,
Arslan Selçuk,
den Hollander Anneke I.,
Birinci Yelda,
Lichtner Peter,
Strom Tim M.,
Toraman Bayram,
Hoefsloot Lies H.,
Cremers Cor W.R.J.,
Brunner Han G.,
Cremers Frans P.M.,
Karaguzel Ahmet,
Kremer Hannie
Publication year - 2007
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20510
Subject(s) - genetics , biology , missense mutation , nonsense mutation , locus (genetics) , hearing loss , allele , auditory neuropathy , gene , mutation , medicine , audiology
Abstract In a consanguineous Turkish family, a locus for autosomal recessive nonsyndromic hearing impairment (ARNSHI) was mapped to chromosome 2q31.1–2q33.1. Microsatellite marker analysis in the complete family determined the critical linkage interval that overlapped with DFNB27, for which the causative gene has not yet been identified, and DFNB59, a recently described auditory neuropathy caused by missense mutations in the DFNB59 gene. The 352–amino acid (aa) DFNB59 gene product pejvakin is present in hair cells, supporting cells, spiral ganglion cells, and the first three relays of the afferent auditory pathway. A novel homozygous nonsense mutation (c.499C>T; p.R167X) was detected in the DFNB59 gene, segregating with the deafness in the family. The mRNA derived from the mutant allele was found not to be degraded in lymphocytes, indicating that a truncated pejvakin protein of 166 aa may be present in the affected individuals. Screening of 67 index patients from additional consanguineous Turkish families with autosomal recessive hearing impairment revealed a homozygous missense mutation (c.547C>T; p.R183W) that segregates with the hearing impairment in one family. Furthermore, in a panel of 83 Dutch patients, two additional novel mutations (c.509_512delCACT; p.S170CfsX35 and c.731T>G; p.L244R), which were not present in ethnically matched controls, were found heterozygously. Together, our data indicate that also nonsense mutations in DFNB59 cause nonsyndromic hearing loss, but that mutations in DFNB59 are not a major cause of nonsyndromic hearing impairment in the Turkish and Dutch population. Hum Mutat 28(7), 718–723, 2007. © 2007 Wiley‐Liss, Inc.