title: Genetic Linkage Analysis of DFNB3, DFNB9 and DFNB21 Loci in GJB2 Negative Families with Autosomal Recessive Non-syndromic Hearing Loss.
abstract: BACKGROUND
  Autosomal recessive non-syndromic hearing loss (ARNSHL) is the most common hereditary form of deafness, and exhibits a great deal of genetic heterogeneity. So far, more than seventy various DFNB loci have been mapped for ARNSHL by linkage analysis. The contribution of three common DFNB loci including DFNB3, DFNB9, DFNB21 and gap junction beta-2 (GJB2) gene mutations in ARNSHL was investigated in south of Iran for the first time.
  
  
  METHODS
  In this descriptive study, we investigated sixteen large families with at least two affected individuals. After DNA extraction, GJB2 gene mutations were analyzed using direct sequencing method. Negative samples for GJB2 gene mutations were analyzed for the linkage to DFNB3, DFNB9 and DFNB21 loci by genotyping the corresponding short tandem repeat (STR) markers using polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) methods.
  
  
  RESULTS
  GJB2 mutations (283G>A and 29delT) were causes of hearing loss in 12.5% of families with ARNSHL and no evidence of linkage were found for any of DFNB3, DFNB9 and DFNB21 loci.
  
  
  CONCLUSIONS
  GJB2 mutations are associated with ARNSHL. We failed to find linkage of the DFNB3, DFNB9 and DFNB21 loci among GJB2 negative families. Therefore, further studies on large-scale population and other loci will be needed to find conclusively linkage of DFNB loci and ARNSHL in the future.
authors.affiliation: Molecular Medicine Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
authors.forename: Marjan
authors.initials: M
authors.lastname: Masoudi
authors.affiliation: Molecular Medicine Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
authors.forename: Najmeh
authors.initials: N
authors.lastname: Ahangari
authors.affiliation: Molecular Medicine Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Poursadegh Zonouzi
authors.affiliation: Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Poursadegh Zonouzi
authors.affiliation: Molecular Medicine Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
authors.forename: Azim
authors.initials: A
authors.lastname: Nejatizadeh
keywords: Autosomal recessive non-syndromic hearing loss; DFNB loci; Genetic linkage analysis