INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
MOLECULAR DIAGNOSIS OF BRACHIO-OTO-RENAL (BOR) SYNDROME IN A FAMILY. NOVEL MUTATION IN THE GENE EYA1.
Autor/es:
DALAMON, VIVIANA; WERNERT, M. FLORENCIA; ELGOYHEN, A. BELEN
Lugar:
Hinxton, Cambridge, UK.
Reunión:
Congreso; 8th Molecular Biology of Hearing and Deafness Conference; 2011
Resumen:
Brachio-Oto-renal (BOR) syndrome is known as one of the most common forms of autosomal dominant syndromic hearing impairement. The phenotype includes hearing loss, auricular and branchial arch malformations and renal anomalies. The penetrance is high but incomplete and the expressivity is variable. Hearing impariment is found in 70 to 93% of affected persons being conductive, sensorineural or mixed; however age of onset may vary from childhood to young adulthood. Genes EYA1 (eyes absent 1) and SIX1 have been associated with the BOR phenotype. They both act in a regulatory network which regulates precursor cell proliferation and survival during mammalian organogenesis. EYA1 encodes a transcriptional co-activator that is widely expressed in the otic vesicle, in the subsequent cochlear and vestibular neuroepithelia, as well as in the developing kidney. SIX1 encodes a transcriptional factor and is co-expressed with EYA in many tissues during mammalian organogenesis. Mutations in EYA1 have been found to be responsible for BOR syndrome in approximately 40% of subjects. Here we report an Argentinean family with BOR syndrome associated with a frameshift mutation in EYA1. We performed clinical and molecular diagnostic testing in 9 members of the family (5 affected subjects with diagnosis of BOR) by performing haplotypes reconstructed by typing three short tandem repeats polymorphisms mapping SIX and EYA1 loci. Segregation was compatible with the EYA1 locus, thus all exons and intronic flanking regions of the gene were sequenced. In all 5 affected members of the family a novel mutation was identified (c.1122delA). The mutation c.1122delA, has not been previously reported and it is predicted to produce a frameshift and consequently a truncated protein (p.Leu374Phefs379X). Clinical features in probands with the mutation included renal alterations and hearing loss. Being a disease of dominant inheritance, we infer that this mutation is responsible for the BOR phenotype in this family.