Short Report: A novel nonsense mutation in the EYA1 gene associated with branchio-oto-renal/branchiootic syndrome in an Afrikaner kindred

• Published in: Clinical genetics 2006-07, Vol.70 (1), p.63
• Main Authors: Clarke, J C, Honey, E M, Bekker, E, Snyman, L C, Raymond, RM, Lord, C, Brophy, P D
• Format: Article
• Language: English
• Subjects: Deafness; Genetic disorders; Kidney diseases; Mutation; Proteins
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2006.00642.x

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized by the associations of hearing loss, branchial arch defects and renal anomalies. Branchiootic (BO) syndrome is a related disorder that presents without the highly variable characteristic renal anomalies of BOR syndrome. Dominant mutations in the human homologue of the Drosophila eyes absent gene (EYA1 ) are frequently the cause of both BOR and BO syndromes. We report a South African family of Afrikaner descent with affected individuals presenting with pre-auricular abnormalities and either hearing loss or bilateral absence of the kidneys. Genetic analysis of the pedigree detected a novel EYA1 heterozygous nonsense mutation in affected family members but not in unaffected family members or a random DNA panel. Through mutational analysis, we conclude that this particular mutation is the cause of BOR/BO syndrome in this family as a result of a truncation of the EYA1 protein that ablates the critical EYA homologous region. To the best of our knowledge, this is the first case of BOR/BO syndrome reported in Africa or in those of the Afrikaner descent. [PUBLICATION ABSTRACT]