Novel TMC1 structural and splice variants associated with congenital nonsyndromic deafness in a Sudanese pedigree

Mutations of the transmembrane channel‐like gene 1 (TMC1) have been shown to cause autosomal dominant and recessive forms of congenital nonsyndromic deafness linked to the loci DFNA36 and DFNB7/B11, respectively. In a Sudanese pedigree affected by an apparently recessive form of nonsyndromic deafnes...

Full description

Saved in:
Bibliographic Details
Published in:Human mutation 2005-01, Vol.25 (1), p.100-100
Main Authors: Meyer, Christian G., Gasmelseed, Nagla M., Mergani, Adil, Magzoub, Mubarak M.A., Muntau, Birgit, Thye, Thorsten, Horstmann, Rolf D.
Format: Article
Language:English
Subjects:
autosomal recessive nonsyndromic deafness
Chromosomes, Human, Pair 9
Connexins
Consanguinity
Deafness
Deafness - congenital
Deafness - genetics
DFNB7/11
DNA Mutational Analysis
Female
Genetic Linkage
Higher education
Humans
Male
Mass spectrometry
Medicine
Membrane Proteins - genetics
Mutation
mutation analysis
Pedigree
RNA Splicing - genetics
Scientific imaging
Sudan
TMC1
transmembrane channel-like gene 1l
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Mutations of the transmembrane channel‐like gene 1 (TMC1) have been shown to cause autosomal dominant and recessive forms of congenital nonsyndromic deafness linked to the loci DFNA36 and DFNB7/B11, respectively. In a Sudanese pedigree affected by an apparently recessive form of nonsyndromic deafness, we performed a linkage analysis using markers covering the deafness loci DFNB1 – DFNB30. A two‐point LOD score of 3.08 was obtained at marker position D9S1876, located within the first intron of the TMC1 gene at DFNB7/B11. By DNA sequencing of TMC1 exons 3‐22, we identified the structural variant c.1165C>T in exon 13, leading to the stop codon p.Arg389X, and the splice‐site variant c.19+5G>A, independently segregating with the deafness phenotype. The c.1165C>T [p.Arg389X] mutation was also observed in four out of 243 unrelated deaf Sudanese individuals, but none of the mutations was found among 292 normal hearing controls. The finding of TMC1 mutations contributing to deafness in Sudan confirms and extends previous reports on the role of TMC1 in recessive nonsyndromic deafness and shows that deafness‐causing TMC1 mutations may occur in various ethnic groups. © 2004 Wiley‐Liss, Inc.
ISSN:1059-7794
1098-1004
DOI:10.1002/humu.9302