Novel partial duplication of EYA1 causes branchiootic syndrome in a large Brazilian family. (September 2015)

• Record Type: Journal Article
• Authors: Dantas, Vitor G.L.; Freitas, Erika L.; Della-Rosa, Valter A.; Lezirovitz, Karina; de Moraes, Ana Maria S.M.; Ramos, Silvia B.; Oiticica, Jeanne; Alves, Leandro U.; Pearson, Peter L.; Rosenberg, Carla; Mingroni-Netto, Regina C.
• Is Part Of: International journal of audiology. Volume 54:Number 9(2015:Sep.)
• Page Start: 593
• Page End: 598
• Publication Date: 2015-09
• Subjects: Audiology -- Periodicals; Hearing disorders -- Periodicals; Deafness -- Prevention -- Periodicals; Hearing Disorders -- Periodicals; Hearing -- Periodicals; 617.8
• Languages: English
• ISSNs: 1499-2027

Abstract

<abstract> <title>Abstract</title> <p> <italic>Objective:</italic> To identify novel genetic causes of syndromic hearing loss in Brazil. <italic>Design:</italic> To map a candidate chromosomal region through linkage studies in an extensive Brazilian family and identify novel pathogenic variants using sequencing and array-CGH. <italic>Study sample:</italic> Brazilian pedigree with individuals affected by BO syndrome characterized by deafness and malformations of outer, middle and inner ear, auricular and cervical fistulae, but no renal abnormalities. <italic>Results:</italic> Whole genome microarray-SNP scanning on samples of 11 affected individuals detected a multipoint Lod score of 2.6 in the EYA1 gene region (chromosome 8). Sequencing of EYA1 in affected patients did not reveal pathogenic mutations. However, oligonucleotide-array-CGH detected a duplication of 71.8Kb involving exons 4 to 10 of EYA1 (heterozygous state). Real-time-PCR confirmed the duplication in fourteen of fifteen affected individuals and absence in 13 unaffected individuals. The exception involved a consanguineous parentage and was assumed to involve a different genetic mechanism. <italic>Conclusions:</italic> Our findings implicate this EYA1 partial duplication segregating with BO phenotype in a Brazilian pedigree and is the first description of a large duplication leading to the BOR/BO syndrome.</p> </abstract>