title: Rare copy number variation in cerebral palsy.
abstract: Recent studies have established the role of rare copy number variants (CNVs) in several neurological disorders but the contribution of rare CNVs to cerebral palsy (CP) is not known. Fifty Caucasian families having children with CP were studied using two microarray designs. Potentially pathogenic, rare (<1% population frequency) CNVs were identified, and their frequency determined, by comparing the CNVs found in cases with 8329 adult controls with no known neurological disorders. Ten of the 50 cases (20%) had rare CNVs of potential relevance to CP; there were a total of 14 CNVs, which were observed in <0.1% (<8/8329) of the control population. Eight inherited from an unaffected mother: a 751-kb deletion including FSCB, a 1.5-Mb duplication of 7q21.13, a 534-kb duplication of 15q11.2, a 446-kb duplication including CTNND2, a 219-kb duplication including MCPH1, a 169-kb duplication of 22q13.33, a 64-kb duplication of MC2R, and a 135-bp exonic deletion of SLC06A1. Three inherited from an unaffected father: a 386-kb deletion of 12p12.2-p12.1, a 234-kb duplication of 10q26.13, and a 4-kb exonic deletion of COPS3. The inheritance was unknown for three CNVs: a 157-bp exonic deletion of ACOX1, a 693-kb duplication of 17q25.3, and a 265-kb duplication of DAAM1. This is the first systematic study of CNVs in CP, and although it did not identify de novo mutations, has shown inherited, rare CNVs involving potentially pathogenic genes and pathways requiring further investigation.
authors.affiliation: Robinson Institute, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Gai
authors.initials: G
authors.lastname: McMichael
authors.affiliation: Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Santhosh
authors.initials: S
authors.lastname: Girirajan
authors.affiliation: Autism and Developmental Medicine Institute, Genomic Medicine Institute, and Department of Pediatrics, Geisinger Health System, Danville, PA, USA.
authors.forename: Andres
authors.initials: A
authors.lastname: Moreno-De-Luca
authors.affiliation: 1] Genetics and Molecular Pathology, SA Pathology at Women's and Children's Hospital, Adelaide, Australia [2] Department of Paediatrics at the Women's and Children's Hospital, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Jozef
authors.initials: J
authors.lastname: Gecz
authors.affiliation: Department of Paediatrics at the Women's and Children's Hospital, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Chloe
authors.initials: C
authors.lastname: Shard
authors.affiliation: Department of Paediatrics at the Women's and Children's Hospital, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Lam Son
authors.initials: LS
authors.lastname: Nguyen
authors.affiliation: Genetics and Molecular Pathology, SA Pathology at Women's and Children's Hospital, Adelaide, Australia.
authors.forename: Jillian
authors.initials: J
authors.lastname: Nicholl
authors.affiliation: Robinson Institute, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Catherine
authors.initials: C
authors.lastname: Gibson
authors.affiliation: South Australian Clinical Genetics Service, SA Pathology at Women's and Children's Hospital, and Discipline of Paediatrics, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Eric
authors.initials: E
authors.lastname: Haan
authors.affiliation: Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Eichler
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Christa Lese
authors.initials: CL
authors.lastname: Martin
authors.affiliation: Robinson Institute, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Alastair
authors.initials: A
authors.lastname: MacLennan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000075686:COP9 Signalosome Complex; D051177:Catenins / Q000235:genetics; D018797:Cell Cycle Proteins; D002547:Cerebral Palsy / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D003598:Cytoskeletal Proteins; D056915:DNA Copy Number Variations / Q000235:genetics*; D005091:Exons; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D046228:Microarray Analysis; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D017384:Sequence Deletion; D020741:rho GTP-Binding Proteins; D000095002:Delta Catenin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C477661:COPS3 protein, human; D051177:Catenins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C499094:DAAM1 protein, human; C460645:MCPH1 protein, human; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D000075686:COP9 Signalosome Complex; D020741:rho GTP-Binding Proteins; D000095002:Delta Catenin; C000722348:CTNND2 protein, human