TY - JOUR
T1 - Rare copy number variation in cerebral palsy
AU - McMichael, Gai
AU - Girirajan, Santhosh
AU - Moreno-De-Luca, Andres
AU - Gecz, Jozef
AU - Shard, Chloe
AU - Nguyen, Lam Son
AU - Nicholl, Jillian
AU - Gibson, Catherine
AU - Haan, Eric
AU - Eichler, Evan
AU - Martin, Christa Lese
AU - MacLennan, Alastair
N1 - Funding Information:
We thank Corinne Reynolds, Dr Michael O′Callaghan, Jessica Broadbent, Drs Ray Russo, James Rice and Andrew Tidemann of the Paediatric Rehabilitation Department at the Women’s and Children’s Hospital, Adelaide for help with case recruitment. We especially thank the families that participated in this study. This study is funded by the Australian National Health and Medical Research Council (Grant No. 1019928), CP Alliance Research Foundation, Women’s and Children’s Hospital Foundation and the National Institute of Health and National Institute of Mental Health (Grant No. 074090-08). DNA/ cell lines were provided by Genetic Repositories Australia, an Enabling Facility supported by the Australian National Health and Medical Research Council (Grant No. 401184).
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
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U2 - 10.1038/ejhg.2013.93
DO - 10.1038/ejhg.2013.93
M3 - Article
C2 - 23695280
AN - SCOPUS:84890791333
SN - 1018-4813
VL - 22
SP - 40
EP - 45
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 1
ER -