Contribution of copy number variants CNVs to congenital, unexplained intellectual and developmental disabilities in Lebanese patientsReportar como inadecuado

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1 Unité de génétique médicale 2 GMGF - Génétique Médicale et Génomique Fonctionnelle 3 Service de pédiatrie 4 Neuropediatrics Department 5 Département de Médecine interne 6 USJ - Université Saint-Joseph de Beyrouth 7 Institut Jérôme Lejeune

Abstract : Background: Chromosomal microarray analysis CMA is currently the most widely adopted clinical test for patients with unexplained intellectual disability ID, developmental delay DD, and congenital anomalies. Its use has revealed the capacity to detect copy number variants CNVs, as well as regions of homozygosity, that, based on their distribution on chromosomes, indicate uniparental disomy or parental consanguinity that is suggestive of an increased probability of recessive disease. Results: We screened 149 Lebanese probands with ID-DD and 99 healthy controls using the Affymetrix Cyto 2.7 M and SNP6.0 arrays. We report all identified CNVs, which we divided into groups. Pathogenic CNVs were identified in 12.1% of the patients. We review the genotype-phenotype correlation in a patient with a 1q44 microdeletion and refine the minimal critical regions responsible for the 10q26 and 16q monosomy syndromes. Several likely causative CNVs were also detected, including new homozygous microdeletions 9p23p24.1, 10q25.2, and 8p23.1 in 3 patients born to consanguineous parents, involving potential candidate genes. However, the clinical interpretation of several other CNVs remains uncertain, including a microdeletion affecting ATRNL1. This CNV of unknown significance was inherited from the patient-s unaffected-mother; therefore, additional ethnically matched controls must be screened to obtain enough evidence for classification of this CNV. Conclusion: This study has provided supporting evidence that whole-genome analysis is a powerful method for uncovering chromosomal imbalances, regardless of consanguinity in the parents of patients and despite the challenge presented by analyzing some CNVs.

Keywords : Affymetrix 27 M Affymetrix 60 Consanguinity Copy number variants Database Intellectual disability Lebanese population INTERSTITIAL DELETION MENTAL-RETARDATION ARRAY-CGH CORPUS-CALLOSUM LONG ARM CRITICAL REGIONS CANDIDATE GENES DE-NOVO DELAY PHENOTYPE

Autor: Nancy Choucair - Joelle Abou Ghoch - Sandra Corbani - Pierre Cacciagli - Cecile Mignon-Ravix - Nabiha Salem - Nadine Jalkh - Sand



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