Copy Number Variations Found in Patients with a Corpus Callosum Abnormality and Intellectual Disability

Solveig Heide, Boris Keren, Thierry Billette de Villemeur, Sandra Chantot-Bastaraud, Christel Depienne, Caroline Nava, Cyril Mignot, Aurélia Jacquette, Eric Fonteneau, Elodie Lejeune, Corinne Mach, Isabelle Marey, Sandra Whalen, Didier Lacombe, Sophie Naudion, Caroline Rooryck, Annick Toutain, Cédric Le Caignec, Damien Haye, Laurence Olivier-Faivre, Alice Masurel-Paulet, Christel Thauvin-Robinet, Fabien Lesne, Anne Faudet, Dorothée Ville, Vincent des Portes, Damien Sanlaville, Jean-Pierre Siffroi, Marie-Laure Moutard, Delphine Héron

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.