Mutations in TMC1 contribute significantly to nonsyndromic autosomal recessive sensorineural hearing loss: A report of five novel mutations
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Tarih
2009
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier Ireland Ltd
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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.
Açıklama
Anahtar Kelimeler
Autosomal Recessive, Consanguinity, Deafness, Hearing Impairment, Hearing Loss
Kaynak
International Journal of Pediatric Otorhinolaryngology
WoS Q Değeri
Q3
Scopus Q Değeri
Q2
Cilt
73
Sayı
5
