<abstract xmlns="http://www.w3.org/1999/xhtml"><p> Intellectual disability (ID) is a common disorder, with major consequences for individual, family and society. Due to clinical and genetic heterogeneity of ID, in about 50% of cases an etiologic diagnosis cannot be established. The aim of this study was to evaluate the ability of a combination of MLPA kits to establish the diagnosis in 369 patients with syndromic ID and normal or uncertain routine karyotype results. All patients were assessed for chromosome imbalance using SALSA MLPA P064 or P096 kits, if the phenotype was suggestive of a microdeletion syndrome (subgroup A - 186 patients), or subtelomeric P036 and P070 kits, if the phenotype was not suggestive of a microdeletion syndrome or if the result of the standard karyotype was uncertain (subgroup B - 183 patients). Abnormal results detected by these kits were further characterized using appropriate follow-up MLPA kits (Telomere Follow-up set, P029-A1, P250-B2, ME028-B1). In subgroup A we identified 25 patients with microdeletions (13.4%). Using subtelomere screening and follow-up kits in subgroup B we detected cryptic rearrangements in 7.5% cases and identified the origin of the unknown material noticed in the standard karyotype in 10 out of 11 patients. Summarizing data from the two groups, the combined use of MLPA kits led to the diagnosis in 10.6% (38/358) patients with normal karyotype. Using follow-up MLPA kits allowed us both to confirm abnormalities and to determine their size, which facilitated the interpretation of the clinical significance of these rearrangements. For laboratories that do not have yet access to microarray technology, using several MLPA kits represents an effective strategy for establishing the diagnosis in ID patients.</p></abstract>

Intellectual disability (ID) is a common disorder, with major consequences for individual, family and society. Due to clinical and genetic heterogeneity of ID, in about 50% of cases an etiologic diagnosis cannot be established. The aim of this study was to evaluate the ability of a combination of MLPA kits to establish the diagnosis in 369 patients with syndromic ID and normal or uncertain routine karyotype results. All patients were assessed for chromosome imbalance using SALSA MLPA P064 or P096 kits, if the phenotype was suggestive of a microdeletion syndrome (subgroup A - 186 patients), or subtelomeric P036 and P070 kits, if the phenotype was not suggestive of a microdeletion syndrome or if the result of the standard karyotype was uncertain (subgroup B - 183 patients). Abnormal results detected by these kits were further characterized using appropriate follow-up MLPA kits (Telomere Follow-up set, P029-A1, P250-B2, ME028-B1). In subgroup A we identified 25 patients with microdeletions (13.4%). Using subtelomere screening and follow-up kits in subgroup B we detected cryptic rearrangements in 7.5% cases and identified the origin of the unknown material noticed in the standard karyotype in 10 out of 11 patients. Summarizing data from the two groups, the combined use of MLPA kits led to the diagnosis in 10.6% (38/358) patients with normal karyotype. Using follow-up MLPA kits allowed us both to confirm abnormalities and to determine their size, which facilitated the interpretation of the clinical significance of these rearrangements. For laboratories that do not have yet access to microarray technology, using several MLPA kits represents an effective strategy for establishing the diagnosis in ID patients.

Detection of chromosomal imbalances using combined MLPA kits in patients with syndromic intellectual disability

Medical Genetics Center, “Sf. Maria” Children’s Hospital, Iaşi, Romania,

Grigore T. Popa” University of Medicine and Pharmacy, Iaşi, Romania

Department of Medical Genetics, “Grigore T. Popa” University of Medicine and Pharmacy, Iaşi, Romania

Medical Genetics Center, “Sf. Maria” Children’s Hospital, Iaşi, Romania

Revista Romana de Medicina de Laborator

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Intellectual disability (ID) is a common disorder, with major consequences for individual, family and society. Due to clinical and genetic heterogeneity of ID,...

Detection of chromosomal imbalances using combined MLPA kits in patients with syndromic intellectual disability

Pubblicato online: 21 giu 2014

Pagine: 157 - 164

Ricevuto: 04 apr 2014

Accettato: 18 mag 2014

DOI: https://doi.org/10.2478/rrlm-2014-0019

© by Roxana Popescu

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.