Mutations in TMC1 contribute significantly to nonsyndromic autosomal recessive sensorineural hearing loss: a report of five novel mutations.

Division of Clinical Molecular Pathology and Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey.

International journal of pediatric otorhinolaryngology 2009 May

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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.

Citation

Asli Sirmaci, Duygu Duman, Hatice Oztürkmen-Akay, Seyra Erbek, Armağan Incesulu, Burcu Oztürk-Hişmi, Z Serap Arici, E Berrin Yüksel-Konuk, Seda Taşir-Yilmaz, Suna Tokgöz-Yilmaz, Filiz Başak Cengiz, Idil Aslan, Müzeyyen Yildirim, Aylin Hasanefendioğlu-Bayrak, Abdullah Ayçiçek, Ismail Yilmaz, Suat Fitoz, Fazilet Altin, Hilal Ozdağ, Mustafa Tekin. Mutations in TMC1 contribute significantly to nonsyndromic autosomal recessive sensorineural hearing loss: a report of five novel mutations. International journal of pediatric otorhinolaryngology. 2009 May;73(5):699-705