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Genet Med. 2018 Feb;20(2):172-180. doi: 10.1038/gim.2017.83. Epub 2017 Aug 3.

De novo and rare inherited copy-number variations in the hemiplegic form of cerebral palsy.

Author information

1
The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
2
Holland Bloorview Kids Rehabilitation Hospital, Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
3
Deep Genomics Inc., Toronto, Ontario, Canada.
4
Department of Pediatrics, Schulich School of Medicine, Western University, London, Ontario, Canada.
5
Division of Neurology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
6
Thames Valley Children's Centre, London, Ontario, Canada.
7
McMaster University, Hamilton, Ontario, Canada.
8
Grandview Children's Centre, Oshawa, Ontario, Canada.
9
ErinoakKids Centre for Treatment and Development, Mississauga, Ontario, Canada.
10
Ottawa Children's Treatment Centre, Ottawa, Ontario, Canada.
11
Hotel Dieu Hospital, Kingston, Ontario, Canada.
12
Department of Pediatric Laboratory Medicine, Genome Diagnostics, The Hospital for Sick Children, Toronto, Ontario, Canada.
13
Department of Molecular Genetics and McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada.

Abstract

PurposeHemiplegia is a subtype of cerebral palsy (CP) in which one side of the body is affected. Our earlier study of unselected children with CP demonstrated de novo and clinically relevant rare inherited genomic copy-number variations (CNVs) in 9.6% of participants. Here, we examined the prevalence and types of CNVs specifically in hemiplegic CP.MethodsWe genotyped 97 unrelated probands with hemiplegic CP and their parents. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs (<0.1% frequency) that might be relevant to CP. We also sequenced exomes of "CNV-positive" trios.ResultsWe detected de novo CNVs and/or sex chromosome abnormalities in 7/97 (7.2%) of probands, impacting important developmental genes such as GRIK2, LAMA1, DMD, PTPRM, and DIP2C. In 18/97 individuals (18.6%), rare inherited CNVs were found, affecting loci associated with known genomic disorders (17p12, 22q11.21) or involving genes linked to neurodevelopmental disorders.ConclusionWe found an increased rate of de novo CNVs in the hemiplegic CP subtype (7.2%) compared to controls (1%). This result is similar to that for an unselected CP group. Combined with rare inherited CNVs, the genomic data impacts the understanding of the potential etiology of hemiplegic CP in 23/97 (23.7%) of participants.

PMID:
28771244
PMCID:
PMC5846809
DOI:
10.1038/gim.2017.83
[Indexed for MEDLINE]
Free PMC Article

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