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. 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

Mehdi Zarrei  1 , Darcy L Fehlings  2 , Karizma Mawjee  2 , Lauren Switzer  2 , Bhooma Thiruvahindrapuram  1 , Susan Walker  1 , Daniele Merico  1   3 , Guillermo Casallo  1 , Mohammed Uddin  1 , Jeffrey R MacDonald  1 , Matthew J Gazzellone  1 , Edward J Higginbotham  1 , Craig Campbell  4 , Gabrielle deVeber  5 , Pam Frid  6 , Jan Willem Gorter  7 , Carolyn Hunt  8 , Anne Kawamura  2 , Marie Kim  9 , Anna McCormick  10 , Ronit Mesterman  7 , Dawa Samdup  11 , Christian R Marshall  1 , Dimitri J Stavropoulos  12 , Richard F Wintle  1 , Stephen W Scherer  1   13
Affiliations

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

Mehdi Zarrei et al. Genet Med. 2018 Feb.

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.

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Conflict of interest statement

The authors declare no conflict of interest. This project was supported by grants from the Ontario Brain Institute (funding in part by the Government of Ontario), Genome Canada, Canada Foundation for Innovation, Canadian Institute for Advanced Research (CIFAR), Government of Ontario, Canadian Institutes of Health Research, The Hospital for Sick Children, and the University of Toronto McLaughlin Centre. D.L.F. holds the Bloorview Children’s Hospital Foundation Chair in Developmental Paediatrics, J.W.G. holds the Scotiabank Chair in Child Health Research. S.W.S. holds the GlaxoSmithKline-CIHR Chair in Genome Sciences at The Hospital for Sick Children and the University of Toronto.

Figures

Figure 1
Figure 1
Pedigrees of selected families (cases C, D, and G) with multiple variants.
Figure 2
Figure 2
Critical exons in genes expressed prenatally are significantly impacted by rare CNVs in 16 different brain regions. The P value is corrected using the Benjamini-Hochberg method. AMY, amygdaloid complex; CBC, cerebellar cortex; V1C, primary visual cortex; STC, posterior (caudal) superior temporal cortex; IPC, posterior inferior parietal cortex; A1C, primary auditory cortex; S1C, primary somatosensory cortex; M1C, primary motor cortex; STR, striatum; DFC, dorsolateral prefrontal cortex; MFC, medial prefrontal cortex; VFC, ventrolateral prefrontal cortex; OFC, orbital frontal cortex; MD, mediodorsal nucleus of thalamus; ITC, inferolateral temporal cortex; HIP, hippocampus.
See this image and copyright information in PMC

References

    1. Colver A, Fairhurst C, Pharoah PO. Cerebral palsy. Lancet 2014;383:1240–1249. - PubMed
    1. Wood E, Rosenbaum P. The gross motor function classification system for cerebral palsy: a study of reliability and stability over time. Dev Med Child Neurol 2000;42:292–296. - PubMed
    1. Basu AP, Pearse J, Kelly S, Wisher V, Kisler J. Early intervention to improve hand function in hemiplegic cerebral palsy. Front Neurol 2014;5:281. - PMC - PubMed
    1. Oskoui M, Gazzellone MJ, Thiruvahindrapuram B et al, Clinically relevant copy number variations detected in cerebral palsy. Nat Commun 2015;6:7949. - PMC - PubMed
    1. Kirton A, Deveber G, Pontigon AM, Macgregor D, Shroff M. Presumed perinatal ischemic stroke: vascular classification predicts outcomes. Ann Neurol 2008;63:436–443. - PubMed

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