Novel partial duplication of EYA1 causes branchiootic syndrome in a large Brazilian family.
OBJECTIVE
To identify novel genetic causes of syndromic hearing loss in Brazil.


METHODS
To map a candidate chromosomal region through linkage studies in an extensive Brazilian family and identify novel pathogenic variants using sequencing and array-CGH.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
* Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo , Brazil.
Vitor G L
VG
Dantas
Erika L
EL
Freitas
Valter A
VA
Della-Rosa
Karina
K
Lezirovitz
Ana Maria S M
AM
de Moraes
Silvia B
SB
Ramos
Jeanne
J
Oiticica
Leandro U
LU
Alves
Peter L
PL
Pearson
Carla
C
Rosenberg
Regina C
RC
Mingroni-Netto
D019280:Branchio-Oto-Renal Syndrome / Q000150:complications / Q000235:genetics*; D001938:Brazil; D003241:Consanguinity; D004423:Ear / Q000002:abnormalities; D005091:Exons; D005260:Female; D020440:Gene Duplication; D046089:Hearing Loss, Mixed Conductive-Sensorineural / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008126:Lod Score; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C104381:EYA1 protein, human; D017027:Protein Tyrosine Phosphatases
Syndromic deafness; array-CGH; copy number variation (CNV); ear malformation; genetic mapping