title: A familial 7q36.3 duplication associated with agenesis of the corpus callosum.
abstract: Small chromosomal duplications involving 7q36.3 have rarely been reported. This clinical report describes four individuals from a three-generation family with agenesis of the corpus callosum (ACC) and a 0.73 Mb duplication of 7q36.3 detected by array CGH. The 7q36.3 duplication involves two genes: RNA Binding Motif Protein 33 (RBM33) and Sonic Hedgehog (SHH). Most affected family members had mild intellectual disability or borderline intellectual functioning, macrocephaly, a broad forehead, and widely spaced eyes. Two individuals had a Chiari type I malformation. This is the first family reported with ACC associated with a small duplication of these genes. While we cannot establish causation for the relationship between any single gene and the ACC in this family, there is a role for SHH in the formation of the corpus callosum through correct patterning and assembly of the commissural plate, and these data concur with vertebrate studies showing that a gain of SHH expands the facial primordium.
authors.affiliation: The University of Newcastle, School of Medicine and Public Health, Newcastle, New South Wales, Australia.
authors.forename: Keith
authors.initials: K
authors.lastname: Wong
authors.affiliation: The University of Queensland, The UQ Centre for Clinical Research, Brisbane, Queensland, Australia.
authors.forename: Randal
authors.initials: R
authors.lastname: Moldrich
authors.affiliation: The University of Newcastle, School of Medicine and Public Health, Newcastle, New South Wales, Australia.|Hunter Genetics, Newcastle, New South Wales, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hunter
authors.affiliation: Paediatrics, School of Medicine, University of Western Sydney, Sydney, New South Wales, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Edwards
authors.affiliation: Faculty of Science, Technology, and Engineering, LaTrobe University, Bundoora, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Finlay
authors.affiliation: Hunter Genetics, Newcastle, New South Wales, Australia.
authors.forename: Sheridan
authors.initials: S
authors.lastname: O'Donnell
authors.affiliation: Department of Radiology, John Hunter Hospital, Newcastle, New South Wales, Australia.
authors.forename: Tom
authors.initials: T
authors.lastname: MacDougall
authors.affiliation: Hunter Area Pathology Service (HAPS), John Hunter Hospital, Newcastle, New South Wales, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bain
authors.affiliation: The University of Newcastle, School of Medicine and Public Health, Newcastle, New South Wales, Australia.|Hunter Genetics, Newcastle, New South Wales, Australia.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kamien
mesh_terms: D000328:Adult; D061085:Agenesis of Corpus Callosum / Q000235:genetics*; D058674:Chromosome Duplication / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D053823:Hedgehog Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D008875:Middle Aged
chemical_list: D053823:Hedgehog Proteins; C509239:SHH protein, human
keywords: Chiari malformation; RBM33; SHH; agenesis of the corpus callosum; chromosome 7q36.3; macrocephaly; sonic hedgehog