Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function

Kurima, Kiyoto; Peters, Lin; Yang, Yandan; Riazuddin, Saima; Ahmed, Zubair M.; Naz, Sadaf; Arnaud, Deidre; Drury, Stacy S.; Mo, Jianhong; Makishima, Tomoko; Ghosh, Manju; Menon, Purnima; Deshmukh, Dilip; Oddoux, Carole; Ostrer, Harry; Khan, S.G.; Riazuddin, Sheikh; Deininger, Prescott L.; Hampton, Lori L.; Sullivan, Stephen N.; Battey, James F.; Keats, Bronya J.B.; Wilcox, Edward R.; Friedman, Thomas B.; Griffith, Andrew J.

doi:10.1038/ng842

Cited by 391 publications

(458 citation statements)

References 35 publications

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“…1 -4 Among all DFNB loci, the most prevalent one is DFNB1 (GJB2 and GJB6 genes, 5 -6 MIM 121011 and 604418) that accounts for up to 50% of recessive cases. Other loci with a significant number of different families associated are DFNB4 (SLC26A4 gene, 7 MIM 605646), DFNB9 (OTOF gene, 8 MIM 603681), DFNB12 (CDH23 gene, 9 MIM 605516), DFNB7/11 (TMC1 gene, 10 MIM 606706), followed by DFNB8/10 (TMPRSS3 gene, 11 MIM 605511) and DFNB3 (MYO15A gene, 12 MIM 602666).…”

Section: Introductionmentioning

confidence: 99%

Unexpected genetic heterogeneity in a large consanguineous Brazilian pedigree presenting deafness

et al. 2007

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Nonsyndromic autosomal recessive deafness accounts for 80% of hereditary deafness. To date, 52 loci responsible for autosomal recessive deafness have been mapped and 24 genes identified. Here, we report a large inbred Brazilian pedigree with 26 subjects affected by prelingual deafness. Given the extensive consanguinity found in this pedigree, the most probable pattern of inheritance is autosomal recessive. However, our linkage and mutational analysis revealed, instead of an expected homozygous mutation in a single gene, two different mutant alleles and a possible third undetected mutant allele in the MYO15A gene (DFNB3 locus), as well as evidence for other causes for deafness in the same pedigree. Among the 26 affected subjects, 15 were homozygous for the novel c.10573delA mutation in the MYO15A gene, 5 were compound heterozygous for the mutation c.10573delA and the novel deletion c.9957_9960delTGAC and one inherited only a single c.10573delA mutant allele, while the other one could not be identified. Given the extensive consanguinity of the pedigree, there might be at least one more deafness locus segregating to explain the condition in some of the subjects whose deafness is not clearly associated with MYO15A mutations, although overlooked environmental causes could not be ruled out. Our findings illustrate a high level of etiological heterogeneity for deafness in the family and highlight some of the pitfalls of genetic analysis of large genes in extended pedigrees, when homozygosity for a single mutant allele is expected.

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Section: Introductionmentioning

confidence: 99%

Unexpected genetic heterogeneity in a large consanguineous Brazilian pedigree presenting deafness

et al. 2007

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“…Kurima et al (2002) except for p.R389X at exon 15 (Meyer et al, 2005). Membrane-spanning domains, evolutionary conservation and functional effect were determined as described in Table 2.…”

Section: Resultsmentioning

confidence: 99%

Novel sequence variants in theTMC1 gene in Pakistani families with autosomal recessive hearing impairment

et al. 2005

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“…71,[80][81][82] TMC1 gene Mutations in the transmembrane cochlear-expressed gene 1 (TMC1), located on chromosome 9q13-21, can also result in both progressive autosomal dominant and autosomal recessive HL (DFNA36 and DFNB7/DFNB11). 83,84 There are eight vertebrate TMC genes on the basis of their sequence homology. 85 This gene (MIM 606706, GeneID 117531) is considered as a transmembrane protein, and its mutations are associated with prelingual and postlingual HL.…”

Section: Tecta Genementioning

confidence: 99%

Genetic causes of nonsyndromic hearing loss in Iran in comparison with other populations

et al. 2010

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Hearing loss (HL) is the most prevalent sensory defect affecting 1 in 500 neonates. Genetic factors are involved in half of the cases. The extreme heterogeneity of HL makes it difficult to analyze and determine the accurate genetic causes of the impairment. Up to now, 10 genes, namely, GJB2, GJB6, SLC26A4, TECTA, PJVK, Col11A2, Myo15A, TMC1, RDX and microRNA (miR-183), have been studied in an Iranian population. The prevalence of HL in Iran was estimated to be 2-3 times higher than that in other parts of the world. Here, the most common bases of congenital nonsyndromic hearing loss (NSHL) are discussed. We reviewed GJB2, GJB6 (large deletion), TECTA, SLC26A4 and PEJVK mutations, and studied their frequencies and distributions in different ethnic groups in 1934, 500, 121, 80 and 34 unrelated families throughout Iran, respectively. GJB2 mutation was the most common factor causing NSHL, with a mean frequency of 18.17% in the Iranian population. The importance of Iran's geographical location in the migration pathway from west to east through the silk route was also highlighted. SLC26A4 and TECTA mutations were the second and third main reasons of HL and accounted for up to 10 and 4% of prelingual HL in Iran, respectively. Mutations in GJB2, SLC26, TECTA and PJVK genes have an important role in HL in Iran and a screening test should be generated for better intervention and diagnosis programs.

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Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function

Cited by 391 publications

References 35 publications

Unexpected genetic heterogeneity in a large consanguineous Brazilian pedigree presenting deafness

Unexpected genetic heterogeneity in a large consanguineous Brazilian pedigree presenting deafness

Novel sequence variants in theTMC1 gene in Pakistani families with autosomal recessive hearing impairment

Genetic causes of nonsyndromic hearing loss in Iran in comparison with other populations

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