Four novel TMC1 (DFNB7/DFNB11) mutations in Turkish patients with congenital autosomal recessive nonsyndromic hearing loss

• Published in: Human mutation Vol. 26; no. 6; p. 591
• Main Authors: Kalay, E., Karaguzel, A., Caylan, R., Heister, A., Cremers, F.P.M., Cremers, C.W.R.J., Brunner, H.G., de Brouwer, A.P.M., Kremer, H.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.12.2005; Hindawi Limited
• Subjects: Amino Acid Sequence; Connexin 26; Connexins - genetics; Deafness; DFNB7/DFNB11; DNA Mutational Analysis; Families & family life; Female; Frameshift Mutation; Genes; Genetic Linkage; Genetic Testing; Haplotypes; Hearing loss; Hearing Loss - congenital; Hearing Loss - genetics; Hearing protection; Humans; Male; Membrane Proteins - chemistry; Membrane Proteins - genetics; Molecular Sequence Data; Mutation; Mutation, Missense; Otolaryngology; Pedigree; Proteins; Sequence Alignment; TMC1; transmembrane channel-like gene 1; Turkey; Netherlands; Turkey
• ISSN: 1059-7794; 1098-1004
• DOI: 10.1002/humu.9384

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 θ=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. © 2005 Wiley‐Liss, Inc.