TY - JOUR
T1 - Mutations in TMC1 are a common cause of DFNB7/11 hearing loss in the Iranian population
AU - Hildebrand, Michael S.
AU - Kahrizi, Kimia
AU - Bromhead, Catherine J.
AU - Shearer, A. Eliot
AU - Webster, Jennifer A.
AU - Khodaei, Hossein
AU - Abtahi, Rezvan
AU - Bazazzadegan, Niloofar
AU - Babanejad, Mojgan
AU - Nikzat, Nooshin
AU - Kimberling, William J.
AU - Stephan, Dietrich
AU - Huygen, Patrick L.M.
AU - Bahlo, Melanie
AU - Smith, Richard J.H.
AU - Najmabadi, Hossein
PY - 2010/12
Y1 - 2010/12
N2 - Objectives: We investigated the cause of autosomal recessive nonsyndromic hearing loss (ARNSHL) that segregated in 2 consanguineous Iranian families. Methods: Otologic and audiometric examinations were performed on affected members of each family. Genome-wide parametric multipoint linkage mapping using a recessive model was performed with Affymetrix 50K GeneChips or short tandem repeat polymorphisms. Direct sequencing was used to confirm the causative mutation in each family. Results: In 2 Iranian families, L-1651 and L-8600606, with ARNSHL that mapped to the DFNB7/11 locus, homozygosity for a reported splice site mutation (c.776+1G>A), and a novel deletion (c.1589-1590delCT; p.S530*) were identified in the TMC1 gene, respectively. Conclusions: Consistent with the previously reported phenotype in DFNB7/11 families, the 2 Iranian families had segregated congenital, profound hearing impairment. However, in family L-1651, one affected family member (IV:3) has milder hearing impairment than expected, suggesting a potential genetic modifier effect. These results indicate that DFNB7/11 is a common form of genetic hearing loss in Iran, because this population is the source of 6 of the 29 TMC1 mutations reported worldwide.
AB - Objectives: We investigated the cause of autosomal recessive nonsyndromic hearing loss (ARNSHL) that segregated in 2 consanguineous Iranian families. Methods: Otologic and audiometric examinations were performed on affected members of each family. Genome-wide parametric multipoint linkage mapping using a recessive model was performed with Affymetrix 50K GeneChips or short tandem repeat polymorphisms. Direct sequencing was used to confirm the causative mutation in each family. Results: In 2 Iranian families, L-1651 and L-8600606, with ARNSHL that mapped to the DFNB7/11 locus, homozygosity for a reported splice site mutation (c.776+1G>A), and a novel deletion (c.1589-1590delCT; p.S530*) were identified in the TMC1 gene, respectively. Conclusions: Consistent with the previously reported phenotype in DFNB7/11 families, the 2 Iranian families had segregated congenital, profound hearing impairment. However, in family L-1651, one affected family member (IV:3) has milder hearing impairment than expected, suggesting a potential genetic modifier effect. These results indicate that DFNB7/11 is a common form of genetic hearing loss in Iran, because this population is the source of 6 of the 29 TMC1 mutations reported worldwide.
KW - DFNB7/11
KW - Deletion
KW - Splice site mutation
KW - TMC1 gene
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U2 - 10.1177/000348941011901207
DO - 10.1177/000348941011901207
M3 - Article
C2 - 21250555
AN - SCOPUS:78649936024
SN - 0003-4894
VL - 119
SP - 830
EP - 835
JO - Annals of Otology, Rhinology and Laryngology
JF - Annals of Otology, Rhinology and Laryngology
IS - 12
ER -