A Deletion Involving the Connexin 30 Gene in Nonsyndromic Hearing Impairment
Ignacio del Castillo, Ph.D., Manuela Villamar, Ph.D., Miguel A. Moreno-Pelayo, Ph.D., Francisco J. del Castillo, Ph.D., Araceli Álvarez, M.Sc., Dolores Tellería, M.Sc., Ibis Menéndez, M.D., and Felipe Moreno, Ph.D.
Background Inherited hearing impairment affects about 1 in 2000newborns. Up to 50 percent of all patients with autosomal recessivenonsyndromic prelingual deafness in different populations havemutations in the gene encoding the gap-junction protein connexin26 (GJB2) at locus DFNB1 on chromosome 13q12. However, a largefraction (10 to 42 percent) of patients with GJB2 mutationshave only one mutant allele; the accompanying mutation has notbeen identified. DFNB1-linked familial cases with no mutationin GJB2 have also been reported.
Methods We evaluated 33 unrelated probands with nonsyndromicprelingual deafness who had only one GJB2 mutant allele. Ninesubjects had evidence of linkage to DFNB1. We used haplotypeanalysis for markers on 13q12 to search for mutations otherthan the one involving GJB2.
Results We identified a 342-kb deletion in the gene encodingconnexin 30 (GJB6), a protein that is reported to be expressedwith connexin 26 in the inner ear. The deletion extended distallyto GJB2, which remained intact. The break-point junction ofthe deletion was isolated and sequenced, and a specific diagnostictest was developed for this common mutation. Twenty-two of the33 subjects were heterozygous for both the GJB6 and GJB2 mutations,including all 9 with evidence of linkage to DFNB1. Two subjectswere homozygous for the GJB6 mutation.
Conclusions A 342-kb deletion in GJB6 is the second most frequentmutation causing prelingual deafness in the Spanish population.Our data suggest that mutations in the complex locus DFNB1,which contains two genes (GJB2 and GJB6), can result in a monogenicor a digenic pattern of inheritance of prelingual deafness.
Source Information
From the Unidad de Genética Molecular, Hospital Ramón y Cajal, Madrid (I.C., M.V., M.A.M.-P., F.J.C., A.A., D.T., F.M.); and the Departamento de Genética, Hospital Pediátrico William Soler, Havana, Cuba (I.M.).
Address reprint requests to Dr. Moreno at the Unidad de Genética Molecular, Hospital Ramón y Cajal, Carretera de Colmenar km. 9, 28034, Madrid, Spain, or at fmoreno{at}hrc.insalud.es.
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