title: Four novel TMC1 (DFNB7/DFNB11) mutations in Turkish patients with congenital autosomal recessive nonsyndromic hearing loss.
abstract: Mutations in the transmembrane channel-like gene 1 (TMC1) cause prelingual autosomal recessive (DFNB7/11) and postlingual progressive autosomal dominant (DFNA36) nonsyndromic hearing loss. To determine the genetic causes of autosomal recessive nonsyndromic hearing loss (ARNSHL) in the northeast and east of Turkey, 65 unrelated families without mutations in the protein coding region of the GJB2 (GJB2-negative) were analyzed. A genomewide scan for homozygosity and linkage analysis in one of these families revealed a 13.2 cM critical region between D9S273 and D9S153 at chromosome 9p13.2-q21.31 with a maximum two-point lod score of 4.00 at theta=0.0 for marker D9S175. TMC1 is in this critical region. Homozygosity screening with intragenic markers for TMC1 in the remaining 64 families suggested involvement of this gene in three additional families. Subsequent sequencing of TMC1 in these four families revealed four novel homozygous mutations, c.776A>G [p.Tyr259Cys], c.821C>T [p.Pro274Leu], c.1334G>A [p.Arg445His], and c.1083_1087delCAGAT [p.Arg362ProfrX6]. Our results indicate that TMC1 mutations account for at least 6% (4/65) of ARNSHL in GJB2-negative Turkish families from the northeast and east of Turkey.
authors.affiliation: Department of Human Genetics, Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands. E.Kalay@antrg.umcn.nl
authors.forename: E
authors.initials: E
authors.lastname: Kalay
authors.forename: A
authors.initials: A
authors.lastname: Karaguzel
authors.forename: R
authors.initials: R
authors.lastname: Caylan
authors.forename: A
authors.initials: A
authors.lastname: Heister
authors.forename: F P M
authors.initials: FP
authors.lastname: Cremers
authors.forename: C W R J
authors.initials: CW
authors.lastname: Cremers
authors.forename: H G
authors.initials: HG
authors.lastname: Brunner
authors.forename: A P M
authors.initials: AP
authors.lastname: de Brouwer
authors.forename: H
authors.initials: H
authors.lastname: Kremer
mesh_terms: D000595:Amino Acid Sequence; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D008040:Genetic Linkage; D005820:Genetic Testing; D006239:Haplotypes; D034381:Hearing Loss / Q000151:congenital / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D016415:Sequence Alignment; D014421:Turkey
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D008565:Membrane Proteins; C451751:TMC1 protein, human; D000072259:Connexin 26