| Autor: |
Stockley, Tracy L., MendozaLondono, Roberto, Propst, Evan J., Sodhi, Sandi, Dupuis, Lucie, Papsin, Blake C. |
| Zdroj: |
American Journal of Medical Genetics. Part A; March 2009, Vol. 149 Issue: 3 p322-327, 6p |
| Abstrakt: |
Branchiootorenal syndrome is a heterogeneous disorder inherited in an autosomal dominant pattern, characterized by branchial arch abnormalities, hearing loss and renal abnormalities, with mutations in EYA1reported in 30–70 of patients. We have applied a molecular testing strategy of sequencing of the complete coding regionflanking intronic regions and multiple ligation probe amplification analysis of EYA1to a pediatric branchiootorenal proband cohort. EYA1mutations were identified in 82 1417 of the probands. We also describe a novel recurrent EYA1mutation c.867 5G > A found in five unrelated affected patients. RNA analysis showed that c.867 5G > A affects EYA1splicing, producing an aberrant mRNA transcript lacking exon 8 and resulting in premature termination in exon 9. The aberrant transcript was present at approximately 50 level of wildtype EYA1mRNA in fibroblasts, and is predicted to encode an EYA1 protein retaining the amino terminal transcriptional coactivator region but lacking the conserved carboxy terminal Eya phosphatase domain. Patients with the c.867 5G > A mutation were found to have more severe renal abnormalities than probands with other mutations in this cohort. Analysis of the c.867 5G > A mutation suggests that certain transcripts of EYA1escape nonsensemediated decay and encode truncated EYA proteins that may be capable of dominantnegative interactions producing distinct phenotypic features within the branchiootorenal spectrum. © 2009 WileyLiss, Inc. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Plný text