title: Clinical comparison of hearing-impaired patients with DFNB1 against heterozygote carriers of connexin 26 mutations.
abstract: OBJECTIVE
  The aim of the study is to assess clinical characteristics of individuals with nonsyndromic sensorineural hearing loss (NSSNHL) with genetic mutations in GJB2 and/or GJB6. We describe and compare one group with biallelic mutations against a group of heterozygote mutation carriers.
  
  
  METHODS
  A total of 350 patients between the ages of 3 months and 80 years referred to a tertiary care outpatient otology practice for NSSNHL were screened for genetic mutations. Direct sequencing of GJB2 and polymerase chain reaction analysis of GJB6 was performed and clinical data from history and physical, audiologic testing and radiographic studies were reviewed.
  
  
  RESULTS
  Thirty-two patients were found to have biallelic mutations (incidence of 9.1%). Twenty-five patients were found to have only one GJB2 mutation (incidence of 7.1%). Severe to profound hearing loss occurred in 85% of the homozygote group and 38% of the heterozygote group. Both groups similarly had a propensity toward bilateral, symmetric, nonprogressive hearing loss with rare inner ear malformations on radiologic imaging.
  
  
  CONCLUSIONS
  These two patient populations have similar incidences in a cohort of patients evaluated for NSSNHL, which is higher than general population heterozygote carrier rates. Heterozygote mutation carriers had less hearing impairment, but most other factors demonstrated no differences. These results support the theory of an unidentified genetic factor contributing to hearing loss in some heterozygote carriers. Therefore, genetic counseling should consider the complexity of their genetic factors and the limitations of current screening.
authors.affiliation: Department of Otolaryngology, University of Miami, Miami, Florida 33136, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lipan
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Ouyang
authors.forename: Denise
authors.initials: D
authors.lastname: Yan
authors.forename: Simon
authors.initials: S
authors.lastname: Angeli
authors.forename: Li Lin
authors.initials: LL
authors.lastname: Du
authors.forename: Xue-Zhong
authors.initials: XZ
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001301:Audiometry, Pure-Tone; D002648:Child; D002675:Child, Preschool; D003054:Cochlear Implants; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D005838:Genotype; D006310:Hearing Aids; D006312:Hearing Loss, Bilateral / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000534:rehabilitation; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000075302:Connexin 30; D017630:Connexins; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; D000072259:Connexin 26