Current progress of genetic and epigenetic studies of cerebral palsy


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Cerebral palsy (CP) is a heterogeneous condition, with cases sharing the common feature of non-progressive dysfunction of movement and posture. Although widely studied, the etiology of CP is not yet well understood. It is believed that most cases of CP arise from intrauterine injury to the developing brain. Increasing evidence suggests that (epi)genetic factors might collectively account for a large number of CP cases. In this mini-review, we focus mainly on the genetic and epigenetic aspects of recent progress in understanding the etiology of CP.

Full Text

Restricted Access

About the authors

Shen Chen

Beijing Pediatric Research Institute; Beijing Children's Hospital; Capital Medical University; National Center for Children's Health

Email: shenchenlll0@l26.com

Zhong Nanbert

Nanfang Hospital, Southern Medical University; The Third Affiliated Hospital, Guangzhou Medical University; New York State Institute for Basic Research in Developmental Disabilities

Email: Nanbert.Zhong@opwdd.ny.gov

References

  1. Colver A., Fairhurst C., Pharoah P.O. Cerebral palsy. Lancet. 2014; 383(9924): 1240-9.
  2. Graham H.K., Rosenbaum P., Paneth N., Dan B., Lin J.P., Damiano D.L. et al. Cerebral palsy. Nat. Rev. Dis. Primers. 2016; 2: 15082. https://dx.doi. org/10.1038 / nrdp.2015.82.
  3. Yuan J., Wang J., Ma J., Zhu D., Zhang Z., Li J. Paediatric cerebral palsy prevalence and high-risk factors in Henan Province, Central China. J. Rehabil. Med. 2019; 51(1): 47-53. https://dx.doi.org/10.2340/16501977-2486
  4. Wang F., Cai Q., Shi W., Jiang H., Li N., Ma D. et al. A cross-sectional survey of growth and nutritional status in children with cerebral palsy in west China. Pediatr. Neurol. 2016; 58: 90-7. https://dx.doi.org/10.1016/j. pediatrneurol.2016.01.002.
  5. Asgarshirazi M., Farokhzadeh-Soltani M., Keihanidost Z., Shariat M. Evaluation of feeding disorders including gastro-esophageal reflux and oropharyngeal dysfunction in children with cerebral palsy. J. Fam. Reprod. Health. 2017; 11(4): 197-201.
  6. Mei C., Reilly S., Reddihough D., Mensah F., Green J., Morgan PL. Activities and participation of children with cerebral palsy: Parent perspectives. Disabil. Rehabil. 2015; 37(23): 2164-73.
  7. McIntyre S., Badawi N., Brown C., Blair E. Population case-control study of cerebral palsy: Neonatal predictors for low-risk term singletons. Pediatrics. 2011; 127:e667-73.
  8. Mallard C., Davidson J.O., Tan S., Green C.R., Bennet L., Robertson N.J., Gunn A.J. Astrocytes and microglia in acute cerebral injury underlying cerebral palsy associated with preterm birth. Pediatr. Res. 2014; 75(1-2): 234-40.
  9. Torres-Merino S., Moreno-Sandoval H.N., Thompson-Bonilla M.D.R, Leon J.A.O., Gomez-Conde E., Leon-Chavez B.A. et al. Association between rs3833912/rs16944 SNPs and risk for cerebral palsy in Mexican children. Mol. Neurobiol. 2019; 56(3): 1800-11. https://dx.doi.org/10.1007/s12035-018-1178-6.
  10. Shang Q., Zhou C., Liu D., Li W., Chen M., Xu Y. et al. Association between osteopontin gene polymorphisms and cerebral palsy in a Chinese population. Neuromolecular Med. 2016; 18(2): 232-8. https://dx.doi.org/10.1007/s12017-016-8397-7.
  11. Khankhanian P., Baranzini S.E., Johnson B.A., Madireddy L., Nickles D., Croen L.A., Wu Y.W. Sequencing of the IL6 gene in a case-control study of cerebral palsy in children. BMC Med. Genet. 2013; 14: 126. https://dx.doi. org/10.1186/1471-2350-14-126.
  12. Bi D., Chen M., Zhang X., Wang H., Xia L., Shang Q. et al. The association between sex-related interleukin-6 gene polymorphisms and the risk for cerebral palsy. J. Neuroinflammation. 2014; 11: 100. https://dx.doi.org/10.1186/1742-2094-11-100.
  13. Hollegaard M. V, Skogstrand K., Thor sen P., Norgaard- Pedersen B., Hougaard D.M., Grove J. Joint analysis of SNPs and proteins identifies regulatory IL18 gene variations decreasing the chance of spastic cerebral palsy. Hum. Mutat. 2013; 34(1): 143-8. https://dx.doi.org/10.1002/humu.22173.
  14. Yu T., Xia L., Bi D., Wang Y., Shang Q., Zhu D. et al. Association of NOS1 gene polymorphisms with cerebral palsy in a Han Chinese population: A case-control study. BMC Med. Genomics. 2018; 11(1): 56. https://dx.doi.org/10.1186/ s12920-018-0374-6.
  15. Shi W., Zhu Y., Zhou M., Ruan Y., Chen X., Chen X. Malectin gene polymorphisms promote cerebral palsy via M2-like macrophage polarization. Clin. Genet. 2018; 93(4): 794-9. https://dx.doi.org/10.1111/cge.13149.
  16. Bi D., Wang H., Shang Q., Xu Y., Wang F., Chen M. et al. Association of COL4A1 gene polymorphisms with cerebral palsy in a Chinese Han population. Clin. Genet. 2016; 90(2): 149-55. https://dx.doi.org/10.1111/cge.12723.
  17. O’Callaghan M.E., Maclennan A.H., Gibson C.S., McMichael G.L., Haan E.A., Broadbent J.L. et al. Genetic and clinical contributions to cerebral palsy: a multivariable analysis. J. Paediatr. Child Health. 2013; 49(7): 575-81. https://dx.doi. org/10.1111/jpc.12279.
  18. Kallankari H, Huusko J.M., Kaukola T., Ojaniemi M., Mahlman M., Marttila R. et al. Cerebral palsy and polymorphism of the chemokine CCL18 in very preterm children. Neonatology. 2015; 108(2): 124-9. https://dx.doi. org/10.1159/000430765.
  19. Stoknes M., Lien E., Andersen G.L., Bao Y., Blackman J.A., Lie R.T., Vik T. Child apolipoprotein E gene variants and risk of cerebral palsy: Estimation from case-parent triads. Eur. J. Paediatr. Neurol. 2015; 19(3): 286-91. https://dx.doi. org/10.1016/j.ejpn.2014.12.017.
  20. Sun L., Xia L., Wang M., Zhu D., Wang Y., Bi D. et al. Variants of the OLIG2 gene are associated with cerebral palsy in Chinese Han infants with hypoxic-ischemic encephalopathy. Neuromolecular Med. 2019; 21(1): 75-84. https:// dx.doi.org/10.1007/s12017-018-8510-1.
  21. Tuysuz B., Bilguvar K., Koger N., Yalginkaya C., Qaglayan O., Gul E. et al. Autosomal recessive spastic tetraplegia caused by AP4M1 and AP4B1 gene mutation: Expansion of the facial and neuroimaging features. Am. J. Med. Genet. A. 2014; 164A(7): 1677-85. https://dx.doi.org/10.1002/ ajmg.a.36514.
  22. Kruer M.C., Jepperson T., Dutta S., Steiner R.D., Cottenie E., Sanford L. et al. Mutations in y adducin are associated with inherited cerebral palsy. Ann. Neurol. 2013; 74(6): 805-14.
  23. Jameel M., Klar J., Tariq M., Moawia A., Altaf Malik N., Seema Waseem S. et al. A novel AP4M1 mutation in autosomal recessive cerebral palsy syndrome and clinical expansion of AP-4 deficiency. BMC Med. Genet. 2014; 15: 133. https:// dx.doi.org/10.1186/s12881-014-0133-2.
  24. McMichael G., Bainbridge M.N., Haan E., Corbett M., Gardner A., Thompson S. et al. Whole-exome sequencing points to considerable genetic heterogeneity of cerebral palsy. Mol. Psychiatry. 2015; 20(2): 176-82.
  25. Parolin Schnekenberg R., Perkins E.M., Miller J.W., Davies W.I., D’Adamo M.C., Pessia M. et al. De novo point mutations in patients diagnosed with ataxic cerebral palsy. Brain. 2015; 138(Pt 7): 1817-32.
  26. McMichael G., Haan E., Gardner A., Yap T.Y., Thompson S., Ouvrier R. et al. NKX2-1 mutation in a family diagnosed with ataxic dyskinetic cerebral palsy. Eur. J. Med. Genet. 2013; 56(9): 506-9.
  27. Rainier S., Sher C., Reish O., Thomas D., Fink J.K. De novo occurrence of novel SPG3A/atlastin mutation presenting as cerebral palsy. Arch. Neurol. 2006; 63(3): 445-7.
  28. Tessa A, Battini R., Rubegni A., Storti E., Marini C., Galatolo D. et al. Identification of mutations in AP4S1/SPG52 through next generation sequencing in three families. Eur. J. Neurol. 2016; 23(10): 1580-7.
  29. Lerer I., Sagi M., Meiner V., Cohen T., Zlotogora J., Abeliovich D. Deletion of the ANKRD15 gene at 9p24.3 causes parent-of-origin-dependent inheritance of familial cerebral palsy. Hum. Mol. Genet. 2005; 14(24): 3911-20.
  30. Oskoui M., Gazzellone M.J., Thiruvahindrapuram B., Zarrei M., Andersen J., Wei J. et al. Clinically relevant copy number variations detected in cerebral palsy. Nat. Commun. 2015; 6: 7949. https://dx.doi.org/10.1038/ncomms8949.
  31. Zarrei M., Fehlings D.L., Mawjee K., Switzer L., Thiruvahindrapuram B., Walker S. et al. De novo and rare inherited copy-number variations in the hemiplegic form of cerebral palsy. Genet. Med. 2018; 20(2): 172-80. https:// dx.doi.org/10.1038/gim.2017.83.
  32. Mohandas N., Bass-Stringer S., Maksimovic J., Crompton K., Loke Y.J., Walstab J. et al. Epigenome-wide analysis in newborn blood spots from monozygotic twins discordant for cerebral palsy reveals consistent regional differences in DNA methylation. Clin. Epigenetics. 2018; 10: 25. https://dx.doi. org/10.1186/s13148-018-0457-4.
  33. Jiao Z., Jiang Z., Wang J., Xu H., Zhang Q., Liu S. et al. Whole-genome scale identification of methylation markers specific for cerebral palsy in monozygotic discordant twins. Mol. Med. Rep. 2017; 16(6): 9423-30.
  34. Crowgey E.L., Marsh A.G., Robinson K.G., Yeager S.K., Akins R.E. Epigenetic machine learning: utilizing DNA methylation patterns to predict spastic cerebral palsy. BMC Bioinformatics. 2018; 19(1): 225. https://dx.doi.org/10.1186/ s12859-018-2224-0.
  35. Xiao D., Qu Y., Pan L., Li X., Mu D. MicroRNAs participate in the regulation of oligodendrocytes development in white matter injury. Rev. Neurosci. 2018; 29(2): 151-60.
  36. Li H., Wang X.L., Wu Y.Q., Liu X.M., Li A.M. Correlation of the predisposition of Chinese children to cerebral palsy with nucleotide variation in pri-miR-124 that alters the non-canonical apoptosis pathway. Acta Pharmacol. Sin. 2018; 39(9): 1453-62.
  37. Kubota N., Yokoyama T., Hoshi N., Suyama M. Identification of a candidate enhancer for DMRT3 involved in spastic cerebral palsy pathogenesis. Biochem. Biophys. Res. Commun. 2018; 496(1): 133-9.
  38. Smith L.R., Ponten E., Hedstrom Y., Ward S.R., Chambers H.G., Subramaniam S., Lieber R.L. Novel transcriptional profile in wrist muscles from cerebral palsy patients. BMC Med. Genomics. 2009; 2: 44. https://dx.doi.org/10.1186/1755-8794-2-44.
  39. Smith L.R., Chambers H.G., Subramaniam S., Lieber R.L. Transcriptional abnormalities of hamstring muscle contractures in children with cerebral palsy. PLoS One. 2012; 7(8): e40686.
  40. Zogby A.M., Dayanidhi S., Chambers H.G., Schenk S., Lieber R.L. Skeletal muscle fiber-type specific succinate dehydrogenase activity in cerebral palsy. Muscle Nerve. 2017; 55(1): 122-24. https://dx.doi.org/10.1002/ mus.25379.
  41. Smith D.D., Sagaram D., Miller R., Gyamfi-Bannerman C. Risk of cerebral palsy by gestational age among pregnancies at-risk for preterm birth. J. Matern. Fetal Neonatal Med. 2018; 1-5. https://dx.doi.org/10.1080/ 14767058.2018.1536745.
  42. Tronnes H., Wilcox A.J., Lie R.T., Markestad T., Moster D. Risk of cerebral palsy in relation to pregnancy disorders and preterm birth: A national cohort study. Dev. Med. Child Neurol. 2014; 56(8): 779-85.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2019 Bionika Media

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies