1. Contribution of copy number variants (CNVs) to congenital, unexplained intellectual and developmental disabilities in Lebanese patients
- Author
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Ali Fawaz, Cécile Mignon-Ravix, Tony Ibrahim, Sandra Corbani, Eliane Chouery, Nancy Choucair, Laurent Villard, André Mégarbané, Nadine Jalkh, Pierre Cacciagli, Sandra Sabbagh, Nabiha Salem, Joelle Abou Ghoch, Unité de génétique médicale, Université Saint-Joseph de Beyrouth (USJ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de pédiatrie, Hôpital Hôtel Dieu de France, Neuropediatrics Department, Lebanese International University (LIU), Département de Médecine interne, Hotel-Dieu de France Hospital, Université Saint-Joseph de Beyrouth (USJ), and Institut Jérôme Lejeune
- Subjects
Affymetrix 60 ,Candidate gene ,medicine.medical_specialty ,Affymetrix 2.7 M ,Lebanese population ,Intellectual disability ,CRITICAL REGIONS ,LONG ARM ,Consanguinity ,Disease ,INTERSTITIAL DELETION ,DE-NOVO ,Affymetrix 27 M ,PHENOTYPE ,Biochemistry ,CANDIDATE GENES ,Database ,Genetics ,medicine ,Genetics(clinical) ,Copy-number variation ,Affymetrix 6.0 ,Molecular Biology ,Genetics (clinical) ,Biochemistry, medical ,Copy number variants ,business.industry ,Research ,Biochemistry (medical) ,Cytogenetics ,medicine.disease ,Human genetics ,Uniparental disomy ,CORPUS-CALLOSUM ,3. Good health ,DELAY ,Molecular Medicine ,business ,MENTAL-RETARDATION ,ARRAY-CGH ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - 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. Electronic supplementary material The online version of this article (doi:10.1186/s13039-015-0130-y) contains supplementary material, which is available to authorized users.
- Published
- 2015
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