High carrier frequency of the 35delG deafness mutation in European populations

• Published in: European journal of human genetics : EJHG Vol. 8; no. 1; pp. 19 - 23
• Main Authors: Gasparini, Paolo, Rabionet, Raquel, Barbujani, Guido, Melchionda, Salvatore, Petersen, Michael, Brøndum-Nielsen, Karen, Metspalu, Andres, Oitmaa, Eneli, Pisano, Marina, Fortina, Paolo, Zelante, Leopoldo, Estivill, Xavier
• Format: Journal Article
• Language: English
• Published: Leiden Nature Publishing Group 01-01-2000
• Subjects: Connexin 26; Cystic fibrosis; Deafness; Diagnosis; Founder effect; Genetics; Hearing loss; Infants; Jewish people; Mitochondrial DNA; Mutation; Population; Population studies; Recessive traits; Greece; United Kingdom > UK; United States > US; Europe; Denmark; Italy; Estonia; Spain; Mediterranean Area
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/sj.ejhg.5200406

Congenital deafness accounts for about 1 in 1000 infants and approximately 80% of cases are inherited as an autosomal recessive trait. Recently, it has been demonstrated that connexin 26 (GJB2) gene is a major gene for congenital sensorineural deafness. A single mutation (named 35delG) was found in most recessive families and sporadic cases of congenital deafness, among Caucasoids, with relative frequencies ranging from 28% to 63%. We present here the analysis of the 35delG mutation in 3270 random controls from 17 European countries. We have detected a carrier frequency for 35delG of 1 in 35 in southern Europe and 1 in 79 in central and northern Europe. In addition, 35delG was detected in five out of 376 Jewish subjects of different origin, but was absent in other non-European populations. The study suggests either a single origin for 35delG somewhere in Europe or in the Middle East, and the possible presence of a carrier advantage together with a founder effect. The 35delG carrier frequency of 1 in 51 in the overall European population clearly indicates that this genetic alteration is a major mutation for autosomal recessive deafness in Caucasoids. This finding should facilitate diagnosis of congenital deafness and allow early treatment of the affected subjects.