A novel DFNA5 mutation does not cause hearing loss in an Iranian family.
Mutations in DFNA5 lead to autosomal dominant non-syndromic sensorineural hearing loss that starts at the high frequencies. To date, only three DFNA5 mutations have been described, and although different at the genomic DNA level, all lead to exon 8 skipping at the mRNA level. This remarkable fact has led towards the hypothesis that DFNA5-associated hearing loss is caused by a gain-of-function mutation and not by haplo-insufficiency as previously thought. Here, we describe a fourth DFNA5 mutation: the insertion of a cytosine at nucleotide position 640 (AF073308.1:_c.640insC, AAC69324.1:_p. Thr215HisfsX8). Unlike the previously described mutations, this frameshift mutation truncates the protein in exon 5 of the gene. Although the mutation was found in an extended Iranian family with hereditary hearing loss, it does not segregate with the hearing loss phenotype and is even present in persons with normal hearing. This fact provides further support for the hypothesis that DFNA5-associated hearing loss is caused by a gain-of-function mutation.
Van Laer
Lut
L
Department of Medical Genetics, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B-2610, Antwerp, Belgium. Lut.VanLaer@ua.ac.be.
Meyer
Nicole C
NC
Molecular Otolaryngology Research Laboratories, University of Iowa, Iowa City, IA, USA.
Malekpour
Mahdi
M
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Riazalhosseini
Yasser
Y
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Moghannibashi
Mahdi
M
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Kahrizi
Kimia
K
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Vandevelde
Ann
A
Department of Medical Genetics, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B-2610, Antwerp, Belgium.
Alasti
Fatemeh
F
Department of Medical Genetics, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B-2610, Antwerp, Belgium.
Najmabadi
Hossein
H
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Van Camp
Guy
G
Department of Medical Genetics, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B-2610, Antwerp, Belgium.
Smith
Richard J H
RJH
Molecular Otolaryngology Research Laboratories, University of Iowa, Iowa City, IA, USA.
D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007492:Iran; D008297:Male; D009154:Mutation; D010375:Pedigree; D011960:Receptors, Estrogen / Q000235:genetics*; D000094524:Gasdermins
D011960:Receptors, Estrogen; C111432:GSDME protein, human; D000094524:Gasdermins