title: Mutations in TMC1 contribute significantly to nonsyndromic autosomal recessive sensorineural hearing loss: a report of five novel mutations.
abstract: Genome wide homozygosity mapping using Affymetrix 10K arrays revealed the DFNB7/11 locus including the TMC1 gene in 5 of 35 Turkish families with autosomal recessive nonsyndromic severe to profound congenital or prelingual-onset sensorineural hearing loss (SNHL). Additional 51 families were later screened for co-segregation of the locus with the phenotype using microsatellite markers. GJB2 and mtDNA A1555G mutations were negative in probands from each family. Mutation analysis was performed in families showing co-segregation of autosomal recessive SNHL with haplotypes at the DFNB7/11 locus. A total of six different mutations in seven families were identified, including novel missense alterations, p.G444R (c.1330G>A), p.R445C (c.1333C>T), and p.I677T (c.2030T>C), one novel splice site mutation IVS6+2 T>A (c.64+2T>A), and a novel large deletion of approximately 31kb at the 3' region of the gene including exons 19-24, as well as a previously reported nonsense mutation, p.R34X (c.100C>T). All identified mutations co-segregated with autosomal recessive SNHL in all families and were not found in Turkish hearing controls. These results expand the mutation spectrum of TMC1 with five novel mutations and provide data for the significant contribution of TMC1 mutations in hearing loss.
authors.affiliation: Division of Clinical Molecular Pathology and Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey.
authors.forename: Asli
authors.initials: A
authors.lastname: Sirmaci
authors.forename: Duygu
authors.initials: D
authors.lastname: Duman
authors.forename: Hatice
authors.initials: H
authors.lastname: Oztürkmen-Akay
authors.forename: Seyra
authors.initials: S
authors.lastname: Erbek
authors.forename: Armağan
authors.initials: A
authors.lastname: Incesulu
authors.forename: Burcu
authors.initials: B
authors.lastname: Oztürk-Hişmi
authors.forename: Z Serap
authors.initials: ZS
authors.lastname: Arici
authors.forename: E Berrin
authors.initials: EB
authors.lastname: Yüksel-Konuk
authors.forename: Seda
authors.initials: S
authors.lastname: Taşir-Yilmaz
authors.forename: Suna
authors.initials: S
authors.lastname: Tokgöz-Yilmaz
authors.forename: Filiz Başak
authors.initials: FB
authors.lastname: Cengiz
authors.forename: Idil
authors.initials: I
authors.lastname: Aslan
authors.forename: Müzeyyen
authors.initials: M
authors.lastname: Yildirim
authors.forename: Aylin
authors.initials: A
authors.lastname: Hasanefendioğlu-Bayrak
authors.forename: Abdullah
authors.initials: A
authors.lastname: Ayçiçek
authors.forename: Ismail
authors.initials: I
authors.lastname: Yilmaz
authors.forename: Suat
authors.initials: S
authors.lastname: Fitoz
authors.forename: Fazilet
authors.initials: F
authors.lastname: Altin
authors.forename: Hilal
authors.initials: H
authors.lastname: Ozdağ
authors.forename: Mustafa
authors.initials: M
authors.lastname: Tekin
mesh_terms: D001844:Bone Conduction; D000072259:Connexin 26; D017630:Connexins; D017931:DNA Primers / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D005091:Exons; D006239:Haplotypes; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007438:Introns; D008565:Membrane Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014421:Turkey
chemical_list: D017630:Connexins; D017931:DNA Primers; D004272:DNA, Mitochondrial; C000607042:GJB2 protein, human; D008565:Membrane Proteins; C451751:TMC1 protein, human; D000072259:Connexin 26