Journal article
Carrier Rates in the Midwestern United States for GJB2 Mutations Causing Inherited Deafness
JAMA : the journal of the American Medical Association, Vol.281(23), pp.2211-2216
06/16/1999
DOI: 10.1001/jama.281.23.2211
PMID: 10376574
Abstract
CONTEXT Mutations in the GJB2 gene are the most
common known cause of inherited congenital severe-to-profound deafness.
The carrier frequency of these mutations is not known. OBJECTIVES To determine the carrier rate of deafness-causing
mutations in GJB2 in the midwestern United States and the
prevalence of these mutations in persons with congenital sensorineural
hearing loss ranging in severity from moderate to profound, and to
derive revised data for counseling purposes. DESIGN Laboratory analysis, performed in 1998, of samples from
probands with hearing loss for mutations in GJB2 using an
allele-specific polymerase chain reaction assay, single-strand
conformation polymorphism analysis, and direct sequencing. SETTING AND SUBJECTS Fifty-two subjects younger than 19 years
sequentially referred to a midwestern tertiary referral center for
hearing loss or cochlear implantation, with moderate-to-profound
congenital hearing loss of unknown cause, parental nonconsanguinity,
and nonsyndromic deafness with hearing loss limited to a single
generation; 560 control neonates were screened for the 35delG mutation. MAIN OUTCOME MEASURE Prevalence of mutations in the GJB2
gene by congenital deafness status. RESULTS Of 52 sequential probands referred for congenital
sensorineural hearing loss, 22 (42%) were found to have GJB2
mutations. The 35delG mutation was identified in 29 of the 41 mutant
alleles. Of probands' sibs, all homozygotes and compound heterozygotes
had deafness. Fourteen of 560 controls were 35delG heterozygotes, for a
carrier rate expressed as a mean (SE) of 2.5% (0.66%). The carrier
rate for all recessive deafness-causing GJB2 mutations was
determined to be 3.01% (probable range, 2.54%-3.56%). Calculated
sensitivity and specificity for a screening test based on 35delG
mutation alone were 96.9% and 97.4%, respectively, and observed
values were 94% and 97%, respectively. CONCLUSIONS Our data suggest that mutations in GJB2 are
the leading cause of moderate-to-profound congenital inherited deafness
in the midwestern United States. Screening of the GJB2
mutation can be offered to individuals with congenital deafness with
high sensitivity and specificity by screening only for the 35delG
mutation. A positive finding should establish an etiologic diagnosis
and affect genetic counseling.
Details
- Title: Subtitle
- Carrier Rates in the Midwestern United States for GJB2 Mutations Causing Inherited Deafness
- Creators
- Glenn E GreenDaryl A ScottJoshua M McDonaldGeorge G WoodworthVal C SheffieldRichard J. H Smith
- Resource Type
- Journal article
- Publication Details
- JAMA : the journal of the American Medical Association, Vol.281(23), pp.2211-2216
- Publisher
- American Medical Association
- DOI
- 10.1001/jama.281.23.2211
- PMID
- 10376574
- ISSN
- 0098-7484
- eISSN
- 1538-3598
- Language
- English
- Date published
- 06/16/1999
- Academic Unit
- Statistics and Actuarial Science; Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Biostatistics; Medical Genetics and Genomics; Otolaryngology; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984006452602771
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