title: Exome sequencing identifies recessive CDK5RAP2 variants in patients with isolated agenesis of corpus callosum.
abstract: 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.
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Québec, Canada.
authors.forename: Loubna
authors.initials: L
authors.lastname: Jouan
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Québec, Canada.
authors.forename: Bouchra
authors.initials: B
authors.lastname: Ouled Amar Bencheikh
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Québec, Canada.
authors.forename: Hussein
authors.initials: H
authors.lastname: Daoud
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Québec, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Dionne-Laporte
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Québec, Canada.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Dobrzeniecka
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Québec, Canada.
authors.forename: Dan
authors.initials: D
authors.lastname: Spiegelman
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Québec, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rochefort
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Québec, Canada.
authors.forename: Pascale
authors.initials: P
authors.lastname: Hince
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Québec, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Szuto
authors.affiliation: Department of Psychology, Université de Montréal, Montréal, Québec, Canada.|CHU Sainte-Justine Research Center, Montréal, Québec, Canada.
authors.forename: Maryse
authors.initials: M
authors.lastname: Lassonde
authors.affiliation: Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.|Institut de recherches cliniques de Montréal, Montréal, Québec, Canada.
authors.forename: Marine
authors.initials: M
authors.lastname: Barbelanne
authors.affiliation: Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.|Institut de recherches cliniques de Montréal, Montréal, Québec, Canada.|Division of Experimental Medicine, McGill University, Montréal, Québec, Canada.
authors.forename: William Y
authors.initials: WY
authors.lastname: Tsang
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Québec, Canada.|Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Dion
authors.affiliation: Department of Psychology, Université de Montréal, Montréal, Québec, Canada.|CHU Sainte-Justine Research Center, Montréal, Québec, Canada.
authors.forename: Hugo
authors.initials: H
authors.lastname: Théoret
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Québec, Canada.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D000328:Adult; D061085:Agenesis of Corpus Callosum / Q000175:diagnosis / Q000235:genetics*; D018797:Cell Cycle Proteins; D059472:Exome; D005260:Female; D006579:Heterozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D035781:Siblings
chemical_list: C405929:CDK5RAP2 protein, human; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins