Gene identified in family 1304 with autosomal dominant progressive hearing loss.

<p>A: Schematic physical and genetic maps of DFNA36 locus on the 9q31chromosomal region. The <i>TMC1</i> gene is indicated. B: Schematic structure of <i>TMC1</i> gene. <i>TMC1</i> gene has 24 exons. Mutation of p.M418K and p.G417R locate in exon16, and mutation of p.D572N and p.D572H are in exon19. C: Sequencing chromatograms of <i>TMC1</i> showing the heterozygous substitution, c.1253A>T in affected individuals (upper panel) compared with that of normal control (lower panel). The mutated nucleotides are marked by triangles. The predicted amino acid changes and surrounding ones are indicated above the sequences. D: Multiple amino acid sequences alignment of <i>TMC1</i> and its paralog of <i>TMC2</i> using ClustalW software. The conservation analysis shows that p.M418K(arrow) mutation in <i>TMC1</i> located in a highly conserved position comparing with the corresponding sequences of human, mouse, rat, macaque, dog, pig, chick, human <i>TMC2</i> and mouse <i>Tmc2</i>. E: A schematic diagram of <i>TMC1</i> protein predicted by TMHMM2.0 containing six transmembrane domains, a cytoplasmic N and C termini. All reported DFNA36 mutations or residual are indicated. Mutation of p.M418K found in this study is located in the second extracellular loop between the third and the fourth transmembrane domain.