title: GJB2 mutation spectrum in 209 hearing impaired individuals of predominantly Caribbean Hispanic and African descent.
abstract: OBJECTIVE
  The purpose of the study is to determine whether Caribbean Hispanic and African admixture populations have a paucity of mutations in GJB2, encoding connexin 26.
  
  
  METHODS
  We reported the paucity of mutations in GJB2 and deletions in GJB6 in Caribbean Hispanic and African admixture populations in the Bronx, NY, in 2007 [1]. We have now collected 102 additional probands with non-syndromic sensorineural hearing impairment (NSHI), for a total of 209. We describe here a presentation of the combined data.
  
  
  RESULTS
  Of the 209 probands, 36% have affected family members with NSHI and the rest have sporadic occurrence. Of the familial cases, 43% had a first-degree relative affected, and the remainder a more distant relative. The hearing impairment ranged from unilateral mild to bilateral profound, with 76% exhibiting bilateral NSHI (BLNSHI). The single coding exon of the GJB2 gene was sequenced in 209 probands, PCR screening for del(GJB6-D13S1830) and sequencing of the non-coding exon of GJB2 to look for the known splice site mutation was performed in 32 NSHI patients with a heterozygous variation in GJB2, and multiplex ligation-dependent probe amplification (MLPA) testing of GJB2 and GJB6 exon deletions or amplifications (P163 GJB-WFS1 kit) was done in 70 probands. Eight unrelated individuals had biallelic GJB2 mutations, representing 4% of our entire cohort, or 5% of our probands with BLNSHI. Of 127 probands of Hispanic or African descent with BLNSHI, six (4.7%) had biallelic pathogenic mutations, three (2.3%) had monoallelic mutations and 118 (93%) had no disease-causing mutations in GJB2. At the same time, no major deletions were identified either by PCR screening (del(GJB6-D13S1830)) or by MLPA analysis (GJB2 or GJB6), and no subjects had the known splice site mutation in GJB2.
  
  
  CONCLUSIONS
  These results demonstrate that GJB2 is not the major contributor to the genetic basis of NSHI for the Bronx minority admixture populations.
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, NY 10461, United States.
authors.forename: Jidong
authors.initials: J
authors.lastname: Shan
authors.forename: Janie
authors.initials: J
authors.lastname: Chobot-Rodd
authors.forename: Raquel
authors.initials: R
authors.lastname: Castellanos
authors.forename: Melanie
authors.initials: M
authors.lastname: Babcock
authors.forename: Alan
authors.initials: A
authors.lastname: Shanske
authors.forename: Sanjay R
authors.initials: SR
authors.lastname: Parikh
authors.forename: Bernice E
authors.initials: BE
authors.lastname: Morrow
authors.forename: Joy
authors.initials: J
authors.lastname: Samanich
mesh_terms: D044383:Black People / Q000706:statistics & numerical data*; D017691:Caribbean Region / Q000208:ethnology; D002391:Catchment Area, Health; D002648:Child; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000706:statistics & numerical data; D017353:Gene Deletion; D005820:Genetic Testing; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D006630:Hispanic or Latino / Q000706:statistics & numerical data*; D006801:Humans; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D014481:United States / Q000453:epidemiology; D001741:Black or African American
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26