title: A novel DFNA5 mutation does not cause hearing loss in an Iranian family.
abstract: 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.
authors.affiliation: Department of Medical Genetics, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B-2610, Antwerp, Belgium. Lut.VanLaer@ua.ac.be.
authors.forename: Lut
authors.initials: L
authors.lastname: Van Laer
authors.affiliation: Molecular Otolaryngology Research Laboratories, University of Iowa, Iowa City, IA, USA.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Meyer
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Malekpour
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Riazalhosseini
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Moghannibashi
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Kimia
authors.initials: K
authors.lastname: Kahrizi
authors.affiliation: Department of Medical Genetics, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B-2610, Antwerp, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Vandevelde
authors.affiliation: Department of Medical Genetics, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B-2610, Antwerp, Belgium.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Alasti
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Najmabadi
authors.affiliation: Department of Medical Genetics, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B-2610, Antwerp, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
authors.affiliation: Molecular Otolaryngology Research Laboratories, University of Iowa, Iowa City, IA, USA.
authors.forename: Richard J H
authors.initials: RJH
authors.lastname: Smith
mesh_terms: 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
chemical_list: D011960:Receptors, Estrogen; C111432:GSDME protein, human; D000094524:Gasdermins