1. Genomic imbalances detected by array-CGH in patients with syndromal ocular developmental anomalies
- Author
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Anne-Claude Tabet, Marion Gérard-Blanluet, Brigitte Benzacken, Jacques Elion, Nicolas Chassaing, Eva Pipiras, Serge Amselem, Pierre Bitoun, Céline Dupont, Sandrine Passemard, Annick Toutain, Alain Verloes, Samuel Quentin, Marie Legendre, Laurence Faivre, Andrée Delahaye, Frédérique Gatelais, Sophie Kaltenbach, Séverine Drunat, Pierre Gressens, Azzedine Aboura, Couvet, Sandrine, Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP. Nord - Université Paris Cité, Université Paris Cité (UPCité), Physiopathologie et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Faculté de Médecine Paris-Diderot [Paris], Université Paris Diderot - Paris 7 (UPD7), CHU d'Angers [Département Urgences], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Physiopathologie des maladies génétiques d'expression pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire Histologie Embryologie Cytogénétique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Pharmacogénétique et abords thérapeutiques des maladies héréditaires, and Université des Antilles et de la Guyane (UAG)-Université Paris Diderot - Paris 7 (UPD7)-IFR2-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Adult ,Male ,Adolescent ,ocular developmental anomaly ,[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Genetic counseling ,[SDV]Life Sciences [q-bio] ,Gene Dosage ,16p11.2 deletion ,Biology ,[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics ,Bioinformatics ,Gene dosage ,Genome ,Article ,Genetics ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Humans ,YWHAE ,Copy-number variation ,Eye Abnormalities ,Child ,Gene ,Genetics (clinical) ,Chromosome Aberrations ,Comparative Genomic Hybridization ,Otx Transcription Factors ,Microarray analysis techniques ,Genome, Human ,Forkhead Transcription Factors ,Syndrome ,[SDV] Life Sciences [q-bio] ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,array-CGH ,Human genome ,FOXC1 ,Female ,Comparative genomic hybridization ,OTX2 - Abstract
International audience; In 65 patients, who had unexplained ocular developmental anomalies (ODAs) with at least one other birth defect and/or intellectual disability, we performed oligonucleotide comparative genome hybridisation-based microarray analysis (array-CGH; 105A or 180K, Agilent Technologies). In four patients, array-CGH identified clinically relevant deletions encompassing a gene known to be involved in ocular development (FOXC1 or OTX2). In four other patients, we found three pathogenic deletions not classically associated with abnormal ocular morphogenesis, namely, del(17)(p13.3p13.3), del(10)(p14p15.3), and del(16)(p11.2p11.2). We also detected copy number variations of uncertain pathogenicity in two other patients. Rearranged segments ranged in size from 0.04 to 5.68 Mb. These results show that array-CGH provides a high diagnostic yield (15%) in patients with syndromal ODAs and can identify previously unknown chromosomal regions associated with these conditions. In addition to their importance for diagnosis and genetic counselling, these data may help identify genes involved in ocular development.
- Published
- 2012