IMPE2023 Poster Presentations Growth and Syndromes (15 abstracts)
Diagnostic implementation of the MS-MLPA technique in patients with clinical suspicion of Beckwith-Wiedemann and Silver Russell syndromes.
Casali Barbara 1 , Scaglia Paula 1 , Esnaola Azcoiti María 1 , Braslavsky Débora 1 , Sanguineti Nora 1 , Armando Romina 2 , Villegas Florencia 2 , Keselman Ana 1 , Freire Analia 1 , Grinspon Romina 1 , Vilas Mariana 3 , Rosental Sandra 4,1 , Arberas Claudia 2 , Bergadá Ignacio 1 & Ropelato Gabriela 1
1Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) CONICET – FEI – División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina. 2Servicio de Genética médica, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina. 3Sección de Genética y Neonatología, Maternidad Ramón Sardá, Buenos Aires, Argentina. 4Centro Nacional de Genética Médica Dr Eduardo Castilla, ANLIS, Buenos Aires, Argentina
Introduction: MS-MLPA is a specific and sensitive technique for detecting copy number variants and methylation defects in the regions of interest associated with imprinting diseases as Beckwith-Wiedemann (BWS) and Silver Russell (SRS) syndromes and. Both are growth disorders associated with opposite molecular alterations in the 11p15.5 imprinting locus.
Aim: To analyze the diagnostic efficiency of MS-MLPA in a cohort of patients with clinical suspicion of BWS and SRS.
Patients and Methods: Specific clinical records based on latest consensus scoring system for each syndrome were designed. Patients with a score ≥4 were included. Genomic DNA was isolated from peripheral lymphocytes in all patients. All samples were tested with the probemix ME030 targeting the imprinting center IC1 and IC2 in 11p15.5 and for SRS the probemix ME032 with further probes for the imprinted loci on chromosomes 6, 7, and 14.
Results: 18 patients met the inclusion criteria: 11 with SRS and 7 with BWS. Global MS-MLPA diagnostic efficiency was 61%, 6/11 SRS and 5/7 BWS. All SRS positive cases showed loss of methylation in IC1 (IC1-LOM). One patient showed a mosaicism in the methylation profile, which represents a challenge for diagnostic detection. Positive results for BWS cases were loss of methylation in IC2 (IC2 LOM) in 3 and gain of methylation of IC1 and loss of methylation in IC2, probably reflecting the paternal uniparental disomy, in the remaining 2.
Conclusions: In our hands, MS-MLPA diagnostic efficiency was similar to that previously reported. In case of negative results with high clinical scores it is necessary to explore the presence of mosaicism. Nowadays, molecular diagnosis allows an individualized assessment improving clinical management and genetic counseling. We have not found molecular defects in the patients with SRS using the probes ME032 which containing probes from other imprinted loci, probably because the small number of the patients analyzed. Our results provide evidence that the introduction of standardized patient identification criteria into routine diagnostic work-up facilitate the identification of cases for more focused genetic testing and minimize the diagnostic odyssey of patients with growth disorders.
Article tools
My recent searches
My recently viewed abstracts
Authors
IMPE Abstracts
© Bioscientifica 2025 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more