Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance.
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ABSTRACT:
SUBMITTER: Marsh AP
PROVIDER: S-EPMC5894478 | biostudies-literature | 2017 Apr
REPOSITORIES: biostudies-literature
Publications
Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance.
Marsh Ashley P L AP Heron Delphine D Edwards Timothy J TJ Quartier Angélique A Galea Charles C Nava Caroline C Rastetter Agnès A Moutard Marie-Laure ML Anderson Vicki V Bitoun Pierre P Bunt Jens J Faudet Anne A Garel Catherine C Gillies Greta G Gobius Ilan I Guegan Justine J Heide Solveig S Keren Boris B Lesne Fabien F Lukic Vesna V Mandelstam Simone A SA McGillivray George G McIlroy Alissandra A Méneret Aurélie A Mignot Cyril C Morcom Laura R LR Odent Sylvie S Paolino Annalisa A Pope Kate K Riant Florence F Robinson Gail A GA Spencer-Smith Megan M Srour Myriam M Stephenson Sarah E M SE Tankard Rick R Trouillard Oriane O Welniarz Quentin Q Wood Amanda A Brice Alexis A Rouleau Guy G Attié-Bitach Tania T Delatycki Martin B MB Mandel Jean-Louis JL Amor David J DJ Roze Emmanuel E Piton Amélie A Bahlo Melanie M Billette de Villemeur Thierry T Sherr Elliott H EH Leventer Richard J RJ Richards Linda J LJ Lockhart Paul J PJ Depienne Christel C
Nature genetics 20170227 4
Brain malformations involving the corpus callosum are common in children with developmental disabilities. We identified DCC mutations in four families and five sporadic individuals with isolated agenesis of the corpus callosum (ACC) without intellectual disability. DCC mutations result in variable dominant phenotypes with decreased penetrance, including mirror movements and ACC associated with a favorable developmental prognosis. Possible phenotypic modifiers include the type and location of mut ...[more]
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Project description:Agenesis of the corpus callosum (ACC) is a common brain malformation which can be observed either as an isolated condition or as part of numerous congenital syndromes. Therefore, cognitive and neurological involvements in patients with ACC are variable, from mild linguistic and behavioral impairments to more severe neurological deficits. To date, the underlying genetic causes of isolated ACC remains elusive and causative genes have yet to be identified. We performed exome sequencing on three acallosal siblings from the same non-consanguineous family and identified compound heterozygous variants, p.[Gly94Arg];[Asn1232Ser], in the protein encoded by the CDK5RAP2 gene, also known as MCPH3, a gene previously reported to cause autosomal recessive primary microcephaly. Our findings suggest a novel role for this gene in the pathogenesis of isolated ACC.
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