title: Involvement of DFNB59 mutations in autosomal recessive nonsyndromic hearing impairment.
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.
authors: Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors: Rob W J
authors: RW
authors: Collin
authors: Ersan
authors: E
authors: Kalay
authors: Jaap
authors: J
authors: Oostrik
authors: Refik
authors: R
authors: Caylan
authors: Bernd
authors: B
authors: Wollnik
authors: Selçuk
authors: S
authors: Arslan
authors: Anneke I
authors: AI
authors: den Hollander
authors: Yelda
authors: Y
authors: Birinci
authors: Peter
authors: P
authors: Lichtner
authors: Tim M
authors: TM
authors: Strom
authors: Bayram
authors: B
authors: Toraman
authors: Lies H
authors: LH
authors: Hoefsloot
authors: Cor W R J
authors: CW
authors: Cremers
authors: Han G
authors: HG
authors: Brunner
authors: Frans P M
authors: FP
authors: Cremers
authors: Ahmet
authors: A
authors: Karaguzel
authors: Hannie
authors: H
authors: Kremer
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002889:Chromosomes, Human, Pair 2; D003241:Consanguinity; D017931:DNA Primers; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D006311:Hearing Disorders / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics; D000094524:Gasdermins
chemical_list: D017931:DNA Primers; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C519847:PJVK protein, human; D000094524:Gasdermins