Etiological yield of SNP microarrays in idiopathic intellectual disability |
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| Affiliation: | 1. Hacettepe University, Department of Pediatrics, Ankara, Turkey;2. Hacettepe University, Department of Pediatric Genetics, Ankara, Turkey;3. Hacettepe University, Department of Pediatric Neurology, Ankara, Turkey;4. Hacettepe University, Department of Medical Genetics, Ankara, Turkey;1. Department of Urology, University Hospital Zürich, University of Zurich, Zurich, Switzerland;2. Department of Urology, University Hospital Basel, Basel, Switzerland;1. Department of Paediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;2. Division of Neonatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;3. Department of Obstetrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;4. Department of Child Neurology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 EZ Groningen, The Netherlands;1. Department of Pediatrics, The Ohio State University College of Medicine, Nationwide Children''s Hospital, 700 Children''s Drive, Columbus, OH 43205, USA;2. Department of Pathology and Laboratory Medicine, Cytogenetics/Molecular Genetics Laboratory, Nationwide Children''s Hospital, 700 Children''s Drive, Columbus, OH 43205, USA;3. Department of Pathology, The Ohio State University College of Medicine, 1645 Neil Avenue, Columbus, OH 43210, USA;1. Department of Medical Genetics, Dr Faruk Sükan Maternity and Pediatric Hospital, Konya, Turkey;2. Elvankent Ayyıldız Family Health Center, Ankara, Turkey;3. Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK;1. Department of Neuropediatrics, Hospital Universitario Quirón, Madrid, Spain;2. Department of Neurology, Hospital Universitario Quirón, Madrid, Spain;3. Paediatric Primary Care, Centro de Salud Doctor Cirajas, Madrid, Spain;4. Radiodiagnostics Department, Hospital Universitario Quirón, Madrid, Spain;5. Department of Neuro-radiology, Hospital Universitario Quirón, Madrid, Spain;6. Department of Magnetic Resonance, Hospital Universitario Quirón, Madrid, Spain;7. Department of Neuropediatrics, Hospital Infanta Leonor de Vallecas, Madrid, Spain;8. Department of Neurology, Hospital Universitario Quirón, Madrid, Spain;9. Human Brain Mapping Unit, Complutense University of Madrid, Spain;1. Laboratoire de Cytogénétique et Biologie Cellulaire, CHU Pontchaillou, Rennes, France;2. Laboratoire de Génétique Moléculaire, CHU Pontchaillou, Rennes, France;3. CNRS UMR 6290 (IGDR), Université de Rennes 1, France;4. Service de Génétique Médicale, CHU Hôpital Sud, Rennes, France;5. Laboratoire d''Anatomie et Cytologie Pathologiques, CHU Pontchaillou, Rennes, France |
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| Abstract: | Intellectual disability (ID) has a prevalence of 3% and is classified according to its severity. An underlying etiology cannot be determined in 75–80% in mild ID, and in 20–50% of severe ID. After it has been shown that copy number variations involving short DNA segments may cause ID, genome-wide SNP microarrays are being used as a tool for detecting submicroscopic copy number changes and uniparental disomy. This study was performed to investigate the presence of copy number changes in patients with ID of unidentified etiology. Affymetrix® 6.0 SNP microarray platform was used for analysis of 100 patients and their healthy parents, and data were evaluated using various databases and literature. Etiological diagnoses were made in 12 patients (12%). Homozygous deletion in NRXN1 gene and duplication in IL1RAPL1 gene were detected for the first time. Two separate patients had deletions in FOXP2 and UBE2A genes, respectively, for which only few patients have recently been reported. Interstitial and subtelomeric copy number changes were described in 6 patients, in whom routine cytogenetic tools revealed normal results. In one patient uniparental disomy type of Angelman syndrome was diagnosed. SNP microarrays constitute a screening test able to detect very small genomic changes, with a high etiological yield even in patients already evaluated using traditional cytogenetic tools, offer analysis for uniparental disomy and homozygosity, and thereby are helpful in finding novel disease-causing genes: for these reasons they should be considered as a first-tier genetic screening test in the evaluation of patients with ID and autism. |
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| Keywords: | SNP microarray Intellectual disability Uniparental disomy Subtelomeric rearrangements |
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