title: MLPA analysis for a panel of syndromes with mental retardation reveals imbalances in 5.8% of patients with mental retardation and dysmorphic features, including duplications of the Sotos syndrome and Williams-Beuren syndrome regions.
abstract: MLPA analysis for a panel of syndromes with mental retardation (MRS-MLPA) was used for investigation of 258 mentally retarded and dysmorphic patients with normal conventional karyotypes (P064 probe set, MRC-Holland, for detection of (micro)deletions associated with 1p36-deletion, Sotos, Williams-Beuren, Prader-Willi, Angelman, Miller-Dieker, Smith-Magenis, and 22q11-deletion syndromes). Patients were initially referred for HR-CGH analysis and MRS-MLPA was performed retrospectively. MRS-MLPA analysis revealed imbalances in 15/258 patients (5.8%). Ten deletions were identified, including deletions of 1p36, 5q35 (Sotos syndrome), 7q11 (Williams-Beuren syndrome), 17p11 (Smith-Magenis syndrome), 15q11 (Angelman syndrome) and 22q11. Duplications were detected in 5q35, 7q11, 17p13, 17p11 and 22q11. We reviewed another 170 patients referred specifically for MRS-MLPA analysis. Eighty of these patients were referred with a clinical suspicion of a specific syndrome, which was confirmed in 17 patients (21.3%). The remaining 90 patients were referred because of mental retardation and dysmorphism but without suspicion of a specific syndrome. Seven imbalances, including four duplications, were detected in these 90 patients (7.8%). Clinical data regarding three patients investigated by MRS-MLPA are presented. The imbalances carried by these patients include a small interstitial 1p36 deletion, a small duplication of 5q35 (encompassing the NSD1 gene, which is deleted/mutated in Sotos syndrome) and a duplication of 7q11 (reciprocal of the Williams-Beuren syndrome deletion), respectively. MRS-MLPA allows testing for a number of micro-deletions/-duplications in a single experiment, thereby filling a gap between array techniques and single locus techniques. MRS-MLPA combined with Subtelomeric MLPA represents an attractive first test in a clinical algorithm for mental retardation.
authors.affiliation: Chromosome Laboratory, Department of Clinical Genetics, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen ø, Denmark. maria.kirchhoff@rh.hosp.dk
authors.forename: Maria
authors.initials: M
authors.lastname: Kirchhoff
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Bisgaard
authors.forename: Thue
authors.initials: T
authors.lastname: Bryndorf
authors.forename: Tommy
authors.initials: T
authors.lastname: Gerdes
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D005147:Facial Bones / Q000002:abnormalities*; D005260:Female; D020440:Gene Duplication; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D012189:Retrospective Studies; D013577:Syndrome; D018980:Williams Syndrome / Q000235:genetics*