Análise de marcadores moleculares para o diagnóstico da síndrome de Williams-Beuren / Analysis of microsatellite DNA markers in the diagnosis of Williams- Beuren syndrome

AUTOR(ES)
DATA DE PUBLICAÇÃO

2011

RESUMO

INTRODUCTION: Williams-Beuren syndrome (WBS; OMIM 194050) is caused by hemizygous contiguous gene microdeletions at 7q11.23. Typical facies, supravalvular aortic stenosis (SVAS), mental retardation, overfriendliness and hiperacusis comprise typical symptoms in WBS. The most common deletion is 1.55 Mb, however 1.84 Mb deletion also has been described. Although fluorescence in situ hybridization (FISH) is widely used in the detection of deletion, microsatellite markers are considered highly informative and easily manageable. PURPOSE: Test the microsatellite markers for the diagnosis of WBS, to determine the size and parental origin of microdeletion, compare the clinical characteristics between patients with different sizes of the deletion and parental origin. METHODS: We studied 97 patients with clinical diagnosis of WBS using five microsatellite markers: D7S1870, D7S489, D7S613, D7S2476 and D7S489_A. From the genomic DNA of probands and their parents was performed polymerase chain reaction (PCR), followed by electrophoresis on denaturing polyacrylamide gel (urea, 7.5 M) and the results visualized with silver staining. RESULTS AND DISCUSSION: Using five markers together, the result was informative in all patients. The most informative marker was D7S1870 (78.4%) followed by D7S613 (75.3%), D7S489 (70.1%) and D7S2476 (62.9%). The deletion was found in 84 (86.6%) patients and absent in 13 (13.4%) patients. The deletion of 1.55 Mb was observed in 76/84 patients (90.5%) and 1.84 Mb in 8 / 84 patients (9.5%). The parental origin was maternal in 44/84 patients (52.4%) and paternal in 40/84 patients (47.6%). Abnormalities ocular were more frequent in the patients with a deletion. There were no clinical differences in relation to either the size or parental origin of the deletion, except for SVAS, present in more frequency in the patients with paternal deletion. The results for microsatellite markers were concordant with FISH positive, however, in two patients with negative FISH, the microdeletion was detected only by the markers. CONCLUSION: Using these five selected microsatellite markers was informative in all patients. In two cases, the markers were more efficient than FISH, thus can be considered an alternative method for molecular diagnosis in SWB

ASSUNTO(S)

genetic markers marcadores genéticos polymerase chain reaction (pcr) reação em cadeia da polimerase (pcr) síndrome de williams williams syndrome

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