Solveig Heide1, Boris Keren2, Thierry Billette de Villemeur3, Sandra Chantot-Bastaraud4, Christel Depienne5, Caroline Nava6, Cyril Mignot7, Aurélia Jacquette7, Eric Fonteneau2, Elodie Lejeune2, Corinne Mach2, Isabelle Marey7, Sandra Whalen8, Didier Lacombe9, Sophie Naudion9, Caroline Rooryck9, Annick Toutain10, Cédric Le Caignec11, Damien Haye12, Laurence Olivier-Faivre13, Alice Masurel-Paulet13, Christel Thauvin-Robinet13, Fabien Lesne7, Anne Faudet7, Dorothée Ville14, Vincent des Portes14, Damien Sanlaville15, Jean-Pierre Siffroi4, Marie-Laure Moutard3, Delphine Héron16. 1. APHP, GH Pitié Salpêtrière, Department of genetics, unit of medical genetics, reference center for intellectual disabilities of rare causes, Paris, France; GRC Intellectual Disability and Autism, UPMC, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, Paris, France. Electronic address: solveig.heide@aphp.fr. 2. APHP, GH Pitié-Salpêtrière, Department of genetics, unit of developmental genomic, Paris, France. 3. APHP, Hôpital Armand-Trousseau, Division of pediatric neurology, Paris, France; GRC ConCer-LD, UPMC, Paris, France; Inserm U1141, Paris, France. 4. APHP, Hôpital Armand-Trousseau, Department of genetics, division of chromosomal genetics, Paris, France. 5. Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, Paris, France; APHP, GH Pitié-Salpêtrière, Department of genetics, unit of developmental genomic, Paris, France; Department of translational medicine and neurogenetics, IGBMC, CNRS UMR 7104/INSERM U964, Université de Strasbourg, Illkirch, France; Institute of medical genetics of Alsace, Division of cytogenetics, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 6. Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, Paris, France; APHP, GH Pitié-Salpêtrière, Department of genetics, unit of developmental genomic, Paris, France. 7. APHP, GH Pitié Salpêtrière, Department of genetics, unit of medical genetics, reference center for intellectual disabilities of rare causes, Paris, France. 8. APHP, Hôpital Armand-Trousseau, Department of genetics, Division of clinical genetics, Paris, France. 9. CHU Bordeaux, Division of medical genetics, INSERM U1211, Université de Bordeaux, Bordeaux, France. 10. Hôpital Bretonneau, CHU Tours, Division of genetics, Tours, France. 11. CHU Nantes, Institute of biology, Division of medical genetics, Inserm UMR 915/CNRS ERL3147, Nantes, France. 12. APHP, Hôpital Robert-Debré, Division of medical genetics, Paris, France. 13. CHU Dijon, Hôpital d'enfants, FHU-TRANSLAD, Genetic Center, Dijon, France. 14. HCL, GH Est, Division of pediatric neurology, Bron, France. 15. HCL, Division of genetics, Bron, France; Center of Research in neurosciences of Lyon, Inserm U1028, UMR CNRS 5292, GENDEV Team, Université Claude BernardLyon 1, Lyon, France. 16. APHP, GH Pitié Salpêtrière, Department of genetics, unit of medical genetics, reference center for intellectual disabilities of rare causes, Paris, France; GRC Intellectual Disability and Autism, UPMC, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, Paris, France; APHP, Hôpital Armand-Trousseau, Department of genetics, Division of clinical genetics, Paris, France.
Abstract
OBJECTIVE: To evaluate the role that chromosomal micro-rearrangements play in patients with both corpus callosum abnormality and intellectual disability, we analyzed copy number variations (CNVs) in patients with corpus callosum abnormality/intellectual disability STUDY DESIGN: We screened 149 patients with corpus callosum abnormality/intellectual disability using Illumina SNP arrays. RESULTS: In 20 patients (13%), we have identified at least 1 CNV that likely contributes to corpus callosum abnormality/intellectual disability phenotype. We confirmed that the most common rearrangement in corpus callosum abnormality/intellectual disability is inverted duplication with terminal deletion of the 8p chromosome (3.2%). In addition to the identification of known recurrent CNVs, such as deletions 6qter, 18q21 (including TCF4), 1q43q44, 17p13.3, 14q12, 3q13, 3p26, and 3q26 (including SOX2), our analysis allowed us to refine the 2 known critical regions associated with 8q21.1 deletion and 19p13.1 duplication relevant for corpus callosum abnormality; report a novel 10p12 deletion including ZEB1 recently implicated in corpus callosum abnormality with corneal dystrophy; and) report a novel pathogenic 7q36 duplication encompassing SHH. In addition, 66 variants of unknown significance were identified in 57 patients encompassed candidate genes. CONCLUSIONS: Our results confirm the relevance of using microarray analysis as first line test in patients with corpus callosum abnormality/intellectual disability.
OBJECTIVE: To evaluate the role that chromosomal micro-rearrangements play in patients with both corpus callosum abnormality and intellectual disability, we analyzed copy number variations (CNVs) in patients with corpus callosum abnormality/intellectual disability STUDY DESIGN: We screened 149 patients with corpus callosum abnormality/intellectual disability using Illumina SNP arrays. RESULTS: In 20 patients (13%), we have identified at least 1 CNV that likely contributes to corpus callosum abnormality/intellectual disability phenotype. We confirmed that the most common rearrangement in corpus callosum abnormality/intellectual disability is inverted duplication with terminal deletion of the 8p chromosome (3.2%). In addition to the identification of known recurrent CNVs, such as deletions 6qter, 18q21 (including TCF4), 1q43q44, 17p13.3, 14q12, 3q13, 3p26, and 3q26 (including SOX2), our analysis allowed us to refine the 2 known critical regions associated with 8q21.1 deletion and 19p13.1 duplication relevant for corpus callosum abnormality; report a novel 10p12 deletion including ZEB1 recently implicated in corpus callosum abnormality with corneal dystrophy; and) report a novel pathogenic 7q36 duplication encompassing SHH. In addition, 66 variants of unknown significance were identified in 57 patients encompassed candidate genes. CONCLUSIONS: Our results confirm the relevance of using microarray analysis as first line test in patients with corpus callosum abnormality/intellectual disability.
Authors: Mary C Whitman; Silvio Alessandro Di Gioia; Wai-Man Chan; Alon Gelber; Brandon M Pratt; Jessica L Bell; Thomas E Collins; James A Knowles; Christopher Armoskus; Michele Pato; Carlos Pato; Sherin Shaaban; Sandra Staffieri; Sarah MacKinnon; Gail D E Maconachie; James E Elder; Elias I Traboulsi; Irene Gottlob; David A Mackey; David G Hunter; Elizabeth C Engle Journal: Invest Ophthalmol Vis Sci Date: 2020-08-03 Impact factor: 4.799