Mutations in TMC1 are a Common Cause of DFNB7/11 Hearing Loss in the Iranian Population
MS Hildebrand, K Kahrizi… - Annals of otology …, 2010 - journals.sagepub.com
Annals of otology, rhinology & laryngology, 2010•journals.sagepub.com
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 …
(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 …
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.
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