Identification of three novel TECTA mutations in Iranian families with autosomal recessive nonsyndromic hearing impairment at the DFNB21 locus.
Forty-five consanguineous Iranian families segregating autosomal recessive nonsyndromic hearing loss (ARNSHL) and negative for mutations at the DFNB1 locus were screened for allele segregation consistent with homozygosity by descent (HBD) at the DFNB21 locus. In three families demonstrating HBD at this locus, mutation screening of TECTA led to the identification of three novel homozygous mutations: one frameshift mutation (266delT), a transversion of a cytosine to an adenine (5,211C > A) leading to a stop codon, and a 9.6 kb deletion removing exon 10. In total, six mutations in TECTA have now been described in families segregating ARNSHL. All of these mutations are inactivating and produce a similar phenotype that is characterized by moderate-to-severe hearing loss across frequencies with a mid frequency dip. The truncating nature of these mutations is consistent with loss-of-function, and therefore the existing TECTA knockout mouse mutant represents a good model in which to study DFNB21-related deafness.
Meyer
Nicole C
NC
Department of Otolaryngology, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA.
Alasti
Fatemeh
F
Nishimura
Carla J
CJ
Imanirad
Parisa
P
Kahrizi
Kimia
K
Riazalhosseini
Yasser
Y
Malekpour
Mahdi
M
Kochakian
Nafiseh
N
Jamali
Payman
P
Van Camp
Guy
G
Smith
Richard J H
RJ
Najmabadi
Hossein
H
D001299:Audiometry; D001483:Base Sequence; D000072259:Connexin 26; D017630:Connexins; D003241:Consanguinity; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005192:Family Health; D058851:GPI-Linked Proteins; D005808:Genes, Recessive; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D007492:Iran; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D012689:Sequence Homology, Nucleic Acid
D017630:Connexins; D016326:Extracellular Matrix Proteins; C000607042:GJB2 protein, human; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C491350:TECTA protein, human; D000072259:Connexin 26