title: Large-scale screening of mitochondrial DNA mutations among Iranian patients with prelingual nonsyndromic hearing impairment.
abstract: Hereditary hearing impairment (HI) is a genetically heterogeneous disorder caused by mutations either in nuclear DNA (nDNA) or in mitochondrial DNA (mtDNA). The nDNA mutations account for the majority of prelingual nonsyndromic HI (NSHI). The present survey was conducted to screen for known pathogenic mtDNA mutations including A1555G, A3243G, C1494T, and A7445G to provide an accurate estimate of their prevalence in prelingual NSHI for the first time in the Iranian subpopulations. One thousand unrelated probands with NSHI (including both GJB2-negative and GJB2 heterozygote cases) and 1000 healthy matched controls were investigated using the PCR/RFLP method followed by DNA sequencing to confirm the observed mtDNA mutations. Two of the studied mutations, namely A3243G and A7445G, were each found in a single family (a frequency of 0.1% for each). Mutation screening for A3243G followed by DNA sequencing led to the identification of G3316A substitution, with no prior link to HI. Surprisingly, screening for A3243G in the studied population identified 6 cases (0.6%) in probands and 10 (1%) in normal subjects. A1555G, the most common mtDNA mutation associated with deafness in other populations, was not found in the studied samples. To conclude, our findings indicate G3316A as a nonpathogenic variant in the prelingual NSHI subpopulations of Iran and suggest that mtDNA mutations do not play a major role in the etiology of NSHI in Iran.
authors.affiliation: Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Montazer Zohour
authors.forename: Mohammad Amin
authors.initials: MA
authors.lastname: Tabatabaiefar
authors.forename: Fatemeh Azadegan
authors.initials: FA
authors.lastname: Dehkordi
authors.forename: Effat
authors.initials: E
authors.lastname: Farrokhi
authors.forename: Mohammad Taghi
authors.initials: MT
authors.lastname: Akbari
authors.forename: Morteza Hashemzadeh
authors.initials: MH
authors.lastname: Chaleshtori
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D008403:Mass Screening / Q000379:methods*; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D017630:Connexins; D004272:DNA, Mitochondrial; C000607042:GJB2 protein, human; D000072259:Connexin 26