Detection of deletions at 7q11.23 in Williams-Beuren syndrome by polymorphic markers

Abstract

INTRODUCTION:Williams-Beuren syndrome (WBS; OMIM 194050) is caused by a hemizygous contiguous gene microdeletion at 7q11.23. Supravalvular aortic stenosis, mental retardation, overfriendliness, and ocular and renal abnormalities comprise typical symptoms in WBS. Although fluorescence in situ hybridization is widely used for diagnostic confirmation, microsatellite DNA markers are considered highly informative and easily manageable.OBJECTIVES:This study aimed to test the microsatellite markers for the diagnosis of Williams-Beuren syndrome, 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 Williams-Beuren syndrome using five microsatellite markers: D7S1870, D7S489, D7S613, D7S2476 and D7S489_A.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 microdeletion was present in 84 (86.6%) patients and absent in 13 (13.4%) patients. Maternal deletions were found in 52.4% of patients and paternal deletions in 47.6% of patients. The observed size of deletions was 1.55 Mb in 76/84 patients (90.5%) and 1.84 Mb in 8/84 patients (9.5%). SVAS as well as ocular and urinary abnormalities 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.CONCLUSION:Using these five selected microsatellite markers was informative in all patients, thus can be considered an alternative method for molecular diagnosis in Williams-Beuren syndrome.

Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes

“…A strong maternal bias exists for the NF1 deletion, but studies were small in size. 27,28 For Williams Beuren syndrome (WBS [MIM 194050]), which results from NAHR events between flanking LCRs, or SDs, in chromosomal region 7q11.23, we performed a meta-analysis on existing data [29][30][31][32][33] and found no gender bias of origin for the 7q11.23 deletion among 471 probands: 248 (53%) were of maternal origin and 223 (47%) were of paternal origin (two-tailed p ¼ 0.27). There is, however, an important confounding feature for WBS in that the presence of an inversion polymorphism 32 greatly increases risk of meiotic NAHR events.…”

Sex-specific recombination predicts parent of origin for recurrent genomic disorders

“…We curated studies that reported parental origin of CNV (deletions and duplications) at these loci using a systematic PubMed search and the following set of inclusion criteria: 1) the study detailed parent of origin data within one of the NAHR-mediated loci as designated by Coe et al, 2014 [8], (2) the study reported parent of origin data for non-imprinted loci, (3) data were reported for more than 10 families with affected children, and (4) the study clearly treated monozygotic twins as one meiosis event (Additional File 1: Supplemental Methods and Additional File 2: Table S1). We identi ed six loci for further analysis: 5q35.3 [31,32], 7q11.23 [24,[36][37][38][39][40][41][42], 16p11.2 [26], 17p11.2 [43][44][45], 17q11.2 [27][28][29], 22q11.2 [30,37,[46][47][48][49][50][51]. At a seventh locus (3q29) we generated new data to determine the parent of origin for de novo events.…”

Detecção da microdeleção 7q11.23 por MLPA® e estudo clínico dos pacientes com síndrome de Williams-Beuren

“…Médica (Gilbert-Dussardier et al, 1995;Dutly and Schinzel, 1996;Urban et al, 1996;Dutra et al, 2011). Com essa técnica é possível definir a origem parental do cromossomo que abriga a microdeleção e mapear os pontos de quebra cromossômica.…”