title: High prevalence of the W24X mutation in the gene encoding connexin-26 (GJB2) in Spanish Romani (gypsies) with autosomal recessive non-syndromic hearing loss.
abstract: Molecular testing for mutations in the gene encoding connexin-26 (GJB2) at the DFNB1 locus has become the standard of care for genetic diagnosis and counseling of autosomal recessive non-syndromic hearing impairment (ARNSHI). The spectrum of mutations in GJB2 varies considerably among the populations, different alleles predominating in different ethnic groups. A cohort of 34 families of Spanish Romani (gypsies) with ARNSHI was screened for mutations in GJB2. We found that DFNB1 deafness accounts for 50% of all ARNSHI in Spanish gypsies. The predominating allele is W24X (79% of the DFNB1 alleles), and 35delG is the second most common allele (17%). An allele-specific PCR test was developed for the detection of the W24X mutation. By using this test, carrier frequencies were determined in two sample groups of gypsies from different Spanish regions (Andalusia and Catalonia), being 4% and 0%, respectively. Haplotype analysis for microsatellite markers closely flanking the GJB2 gene revealed five different haplotypes associated with the W24X mutation, all sharing the same allele from marker D13S141, suggesting that a founder effect for this mutation is responsible for its high prevalence among Spanish gypsies.
authors.affiliation: Unidad de Genética Molecular, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Araceli
authors.initials: A
authors.lastname: Alvarez
authors.forename: Ignacio
authors.initials: I
authors.lastname: del Castillo
authors.forename: Manuela
authors.initials: M
authors.lastname: Villamar
authors.forename: Luis A
authors.initials: LA
authors.lastname: Aguirre
authors.forename: Anna
authors.initials: A
authors.lastname: González-Neira
authors.forename: Alicia
authors.initials: A
authors.lastname: López-Nevot
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Moreno-Pelayo
authors.forename: Felipe
authors.initials: F
authors.lastname: Moreno
mesh_terms: D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D018389:Codon, Nonsense; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D034381:Hearing Loss / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D015995:Prevalence; D006178:Romani People / Q000235:genetics*; D013030:Spain / Q000453:epidemiology; D013577:Syndrome
chemical_list: D018389:Codon, Nonsense; D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26