title: Copy Number Variations Found in Patients with a Corpus Callosum Abnormality and Intellectual Disability.
abstract: 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.
  
  
  
  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.
  
  
  
  Our results confirm the relevance of using microarray analysis as first line test in patients with corpus callosum abnormality/intellectual disability.
authors.affiliation: 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.
authors.forename: Solveig
authors.initials: S
authors.lastname: Heide
authors.affiliation: APHP, GH Pitié-Salpêtrière, Department of genetics, unit of developmental genomic, Paris, France.
authors.forename: Boris
authors.initials: B
authors.lastname: Keren
authors.affiliation: APHP, Hôpital Armand-Trousseau, Division of pediatric neurology, Paris, France; GRC ConCer-LD, UPMC, Paris, France; Inserm U1141, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Billette de Villemeur
authors.affiliation: APHP, Hôpital Armand-Trousseau, Department of genetics, division of chromosomal genetics, Paris, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Chantot-Bastaraud
authors.affiliation: 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.
authors.forename: Christel
authors.initials: C
authors.lastname: Depienne
authors.affiliation: 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.
authors.forename: Caroline
authors.initials: C
authors.lastname: Nava
authors.affiliation: APHP, GH Pitié Salpêtrière, Department of genetics, unit of medical genetics, reference center for intellectual disabilities of rare causes, Paris, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Mignot
authors.affiliation: APHP, GH Pitié Salpêtrière, Department of genetics, unit of medical genetics, reference center for intellectual disabilities of rare causes, Paris, France.
authors.forename: Aurélia
authors.initials: A
authors.lastname: Jacquette
authors.affiliation: APHP, GH Pitié-Salpêtrière, Department of genetics, unit of developmental genomic, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Fonteneau
authors.affiliation: APHP, GH Pitié-Salpêtrière, Department of genetics, unit of developmental genomic, Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Lejeune
authors.affiliation: APHP, GH Pitié-Salpêtrière, Department of genetics, unit of developmental genomic, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Mach
authors.affiliation: APHP, GH Pitié Salpêtrière, Department of genetics, unit of medical genetics, reference center for intellectual disabilities of rare causes, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Marey
authors.affiliation: APHP, Hôpital Armand-Trousseau, Department of genetics, Division of clinical genetics, Paris, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Whalen
authors.affiliation: CHU Bordeaux, Division of medical genetics, INSERM U1211, Université de Bordeaux, Bordeaux, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.affiliation: CHU Bordeaux, Division of medical genetics, INSERM U1211, Université de Bordeaux, Bordeaux, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Naudion
authors.affiliation: CHU Bordeaux, Division of medical genetics, INSERM U1211, Université de Bordeaux, Bordeaux, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Rooryck
authors.affiliation: Hôpital Bretonneau, CHU Tours, Division of genetics, Tours, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.affiliation: CHU Nantes, Institute of biology, Division of medical genetics, Inserm UMR 915/CNRS ERL3147, Nantes, France.
authors.forename: Cédric Le
authors.initials: CL
authors.lastname: Caignec
authors.affiliation: APHP, Hôpital Robert-Debré, Division of medical genetics, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Haye
authors.affiliation: CHU Dijon, Hôpital d'enfants, FHU-TRANSLAD, Genetic Center, Dijon, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Olivier-Faivre
authors.affiliation: CHU Dijon, Hôpital d'enfants, FHU-TRANSLAD, Genetic Center, Dijon, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Masurel-Paulet
authors.affiliation: CHU Dijon, Hôpital d'enfants, FHU-TRANSLAD, Genetic Center, Dijon, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.affiliation: APHP, GH Pitié Salpêtrière, Department of genetics, unit of medical genetics, reference center for intellectual disabilities of rare causes, Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Lesne
authors.affiliation: APHP, GH Pitié Salpêtrière, Department of genetics, unit of medical genetics, reference center for intellectual disabilities of rare causes, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Faudet
authors.affiliation: HCL, GH Est, Division of pediatric neurology, Bron, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Ville
authors.affiliation: HCL, GH Est, Division of pediatric neurology, Bron, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: des Portes
authors.affiliation: 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.
authors.forename: Damien
authors.initials: D
authors.lastname: Sanlaville
authors.affiliation: APHP, Hôpital Armand-Trousseau, Department of genetics, division of chromosomal genetics, Paris, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Siffroi
authors.affiliation: APHP, Hôpital Armand-Trousseau, Division of pediatric neurology, Paris, France; GRC ConCer-LD, UPMC, Paris, France; Inserm U1141, Paris, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Moutard
authors.affiliation: 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.
authors.forename: Delphine
authors.initials: D
authors.lastname: Héron
mesh_terms: D000293:Adolescent; D000328:Adult; D061085:Agenesis of Corpus Callosum / Q000235:genetics*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D058674:Chromosome Duplication; D002879:Chromosomes, Human, Pair 10; D002888:Chromosomes, Human, Pair 19; D002893:Chromosomes, Human, Pair 3; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D056915:DNA Copy Number Variations; D005260:Female; D053823:Hedgehog Proteins / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D046228:Microarray Analysis; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D055815:Young Adult; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D053823:Hedgehog Proteins; D000071799:Zinc Finger E-box-Binding Homeobox 1; C485631:HEY1 protein, human; C509239:SHH protein, human; C486307:ZEB1 protein, human
keywords: CNV; SNP array; agenesis of corpus callosum; chromosomal microarray; corpus callosum; dysgenesis of corpus callosum