title: Does universal newborn hearing screening identify all children with GJB2 (Connexin 26) deafness? Penetrance of GJB2 deafness.
abstract: OBJECTIVE
  Deafness is the most common neurosensory defect at birth, and GJB2 (connexin 26) mutations are the most frequent genetic cause of hearing loss in many populations. The hearing loss caused by GJB2 mutations is usually congenital in onset and moderate to profound in degree. Considerable phenotypic variation has been noted however, including two anecdotal cases of apparent non penetrance at birth. The objective of this study is to document nine additional children with two pathogenic GJB2 mutations who had non penetrance of hearing loss at birth.
  
  
  METHODS
  Subjects were identified through a national repository which includes deaf probands ascertained primarily from the United States through the Annual Survey of Deaf and Hard of Hearing Children and Youth conducted at the Research Institute at Gallaudet University. The hearing of each of these children had been screened at birth using standard audiologic techniques. Parents were interviewed and available medical records were reviewed. Testing for GJB2 mutations was performed by PCR and sequencing of the entire coding exon in all nine individuals.
  
  
  RESULTS
  Using parent interviews and medical records, we documented that all nine children passed newborn audiologic hearing screening. The age at which the hearing loss was subsequently identified in these nine children ranged from 12-60 mo. Of these nine children, 3 were compound heterozygotes and six were homozygous for the 35delG mutation in the GJB2 gene.
  
  
  CONCLUSIONS
  These nine cases demonstrate that current newborn hearing screening does not identify all infants with two GJB2 mutations. These cases suggest that the frequency of non penetrance at birth is approximately 3.8% or higher. It is important to consider connexin deafness in any child with recessive nonsyndromic hearing loss as well as simplex cases with no history of other affected family members even when the newborn hearing screening results were within the normal range.
authors.affiliation: Department of Biology, Gallaudet University, Washington, DC 20002, USA. virginia.norris@gallaudet.edu
authors.forename: Virginia W
authors.initials: VW
authors.lastname: Norris
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Arnos
authors.forename: Wendy D
authors.initials: WD
authors.lastname: Hanks
authors.forename: Xia
authors.initials: X
authors.lastname: Xia
authors.forename: Walter E
authors.initials: WE
authors.lastname: Nance
authors.forename: Arti
authors.initials: A
authors.lastname: Pandya
mesh_terms: D001300:Audiometry, Evoked Response; D001301:Audiometry, Pure-Tone; D001309:Auditory Threshold; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005260:Female; D034381:Hearing Loss / Q000151:congenital / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D015997:Neonatal Screening / Q000379:methods*; D017084:Otoacoustic Emissions, Spontaneous; D019683:Penetrance; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26