Mutations in TMC1 are a common cause of DFNB7/11 hearing loss in the Iranian population.
OBJECTIVE
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.
Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USA.
Michael S
MS
Hildebrand
Kimia
K
Kahrizi
Catherine J
CJ
Bromhead
A Eliot
AE
Shearer
Jennifer A
JA
Webster
Hossein
H
Khodaei
Rezvan
R
Abtahi
Niloofar
N
Bazazzadegan
Mojgan
M
Babanejad
Nooshin
N
Nikzat
William J
WJ
Kimberling
Dietrich
D
Stephan
Patrick L M
PL
Huygen
Melanie
M
Bahlo
Richard J H
RJ
Smith
Hossein
H
Najmabadi
D002874:Chromosome Mapping; D034201:Computers, Handheld; D003241:Consanguinity; D003638:Deafness / Q000151:congenital / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D034381:Hearing Loss / Q000151:congenital / Q000235:genetics*; D006801:Humans; D007492:Iran; D008565:Membrane Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D022821:RNA Splice Sites / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
D008565:Membrane Proteins; D022821:RNA Splice Sites; C451751:TMC1 protein, human
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