Mutations in TMC1 contribute significantly to nonsyndromic autosomal recessive sensorineural hearing loss: A report of five novel mutations
| Autor: | Duygu Duman, Suna Tokgoz-Yilmaz, Hatice Ozturkmen-Akay, Seda Taşır-Yılmaz, Fazilet Altın, Asli Sirmaci, Hilal Özdağ, E. Berrin Yüksel-Konuk, Ismail Yilmaz, Müzeyyen Yıldırım, Suat Fitoz, Seyra Erbek, Burcu Öztürk-Hişmi, Mustafa Tekin, Abdullah Ayçiçek, Aylin Hasanefendioğlu-Bayrak, İdil Aslan, Filiz Basak Cengiz, Armagan Incesulu, Z. Serap Arıcı |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Turkey
Hearing loss Hearing Loss Sensorineural Nonsense mutation Locus (genetics) Consanguinity DNA Mitochondrial Polymerase Chain Reaction Connexins otorhinolaryngologic diseases medicine Humans Point Mutation Missense mutation DNA Primers Genetics Splice site mutation business.industry Homozygote Membrane Proteins Exons General Medicine Disease gene identification medicine.disease Introns Pedigree Connexin 26 Phenotype Haplotypes Otorhinolaryngology Pediatrics Perinatology and Child Health Sensorineural hearing loss medicine.symptom business Bone Conduction |
| Zdroj: | International Journal of Pediatric Otorhinolaryngology. 73:699-705 |
| ISSN: | 0165-5876 |
| Popis: | 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.1677T (c.2030T > C), one novel splice site mutation IVS6+2 T > A (c.64+2T > A), and a novel large deletion ofapproximately 31 kb 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. (c) 2009 Elsevier Ireland Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect