Abstract Cerebral palsy is a group of syndromes caused by non-progressive brain injury in the fetus or infant and can cause disabilities in childhood. Etiology of cerebral palsy has always been a hot topic for clinical scientists. More and more studies have shown that genetic factors are closely associated with the development of cerebral palsy. With the development and application of various molecular and biological techniques such as chromosome microarray analysis, genome-wide association study, and whole exome sequencing, new achievements have been made in the genetic research of cerebral palsy. Chromosome abnormalities, copy number variations, susceptibility genes, and single gene mutation associated with the development of cerebral palsy have been identified, which provides new opportunities for the research on the pathogenesis of cerebral palsy. This article reviews the advances in the genetic research on cerebral palsy in recent years.
Oskoui M, Coutinho F, Dykeman J, et al. An update on the prevalence of cerebral palsy:a systematic review and meta-analysis[J]. Dev Med Child Neurol, 2013, 55(6):509-519.
[3]
Van Naarden Braun K, Doernberg N, Schieve L, et al. Birth prevalence of cerebral palsy:a population-based study[J]. Pediatrics, 2016, 137(1):1-9.
[4]
Hemminki K, Li X, Sundquist K, et al. High familial risks for cerebral palsy implicate partial heritable aetiology[J]. Paediatr Perinat Epidemiol, 2007, 21(3):235-241.
[5]
McIntyre S, Blair E, Goldsmith S, et al. Congenital anomalies in cerebral palsy:where to from here?[J]. Dev Med Child Neurol, 2016, 58(Suppl 2):71-75.
[6]
MacLennan AH, Thompson SC, Gecz J. Cerebral palsy:causes, pathways, and the role of genetic variants[J]. Am J Obstet Gynecol, 2015, 213(6):779-788.
[7]
Kadotani T, Watanabe Y, Saito T, et al. A chromosomal study on 100 cases of cerebral palsy[J]. Int J Hum Genet, 2001, 1(2):109-112.
[8]
McMichael G, Girirajan S, Moreno-De-Luca A, et al. Rare copy number variation in cerebral palsy[J]. Eur J Hum Genet, 2014, 22(1):40-45.
[9]
Oskoui M, Gazzellone MJ, Thiruvahindrapuram B, et al. Clinically relevant copy number variations detected in cerebral palsy[J]. Nat Commun, 2015, 6:7949.
[10]
Segel R, Benpazi H, Zeligson S, et al. Copy number variations in cryptogenic cerebral palsy[J]. Neurology, 2015, 84(16):1660-1668.
[11]
Nwabuisi-Heath E, Rebeck GW, Ladu MJ, et al. ApoE4 delays dendritic spine formation during neuron development and accelerates loss of mature spines in vitro[J]. ASN Neuro, 2014, 6(1):e00134.
[12]
Forero DA, López-León S, González-Giraldo Y, et al. APOE gene and neuropsychiatric disorders and endophenotypes:A comprehensive review[J]. Am J Med Genet B Neuropsychiatr Genet, 2016. doi:10.1002/ajmg.b.32516.[Epub ahead of print].
[13]
Meirelles Kalil Pessoa de Barr, Rodrigues CJ, de Barros TE, et al. Presence of apolipoprotein E epsilon4 allele in cerebral palsy[J]. J Pediatr Orthop, 2000, 20(6):786-789.
[14]
Lien E, Andersen GL, Bao Y, et al. Gene sequences regulating the production of ApoE and cerebral palsy of variable severity[J]. Eur J Paediatr Neurol, 2014, 18(5):591-596.
[15]
McMichael GL, Gibson CS, Goldwater PN, et al. Association between Apolipoprotein E genotype and cerebral palsy is not confirmed in a Caucasian population[J]. Hum Genet, 2008, 124(4):411-416.
[16]
Xu Y, Wang H, Sun Y, et al. The association of apolipoprotein E gene polymorphisms with cerebral palsy in Chinese infants[J]. Mol Genet Genomics, 2014, 289(3):411-416.
[17]
Mayer-Pickel K, Eberhard K, Lang U, et al. Pregnancy outcome in women with obstetric and thrombotic antiphospholipid syndrome-a retrospective analysis and a review of additional treatment in pregnancy[J]. Clin Rev Allergy Immunol, 2017, 53(1):54-67.
Turedi YA, Sutcu R, Koroglu M, et al. The role of prothrombotic factors in children with hemiplegic cerebral palsy[J]. Minerva Pediatr, 2015, 67(4):279-284.
[20]
Hou R, Ren X, Wang J, et al. TNF-α and MTHFR polymorphisms associated with cerebral palsy in Chinese infants[J]. Mol Neurobiol, 2016, 53(10):6653-6658.
[21]
Kopyta IA, Emich-Widera E, Balcerzyk A, et al. Polymorphisms of genes encoding coagulation factors Ⅱ, V, VⅡ, and XⅢ in relation to pediatric ischemic stroke:family-based and case-control study[J]. Neurologist, 2012, 18(5):282-286.
[22]
Arenas-Sordo ML, Zavala-Hernandez C, Casiano-Rosas C, et al. Leiden V factor and spastic cerebral palsy in Mexican children[J]. Genet Test Mol Biomarkers, 2012, 16(8):978-980.
Cordeiro CN, Tsimis M, Burd I. Infections and brain development[J]. Obstet Gynecol Surv, 2015, 70(10):644-655.
[25]
Wu J, Li X. Plasma tumor necrosis factor-alpha (TNF-α) levels correlate with disease severity in spastic diplegia, triplegia, and quadriplegia in children with cerebral palsy[J]. Med Sci Monit, 2015, 21:3868-3874.
[26]
Kuban KC, O'Shea TM, Allred EN, et al. Systemic inflammation and cerebral palsy risk in extremely preterm infants[J]. J Child Neurol, 2014, 29(12):1692-1698.
[27]
Bi D, Chen M, Zhang X, et al. The association between sex-related interleukin-6 gene polymorphisms and the risk for cerebral palsy[J]. J Neuroinflammation, 2014, 11:100.
[28]
Varner MW, Marshall NE, Rouse DJ, et al. The association of cord serum cytokines with neurodevelopmental outcomes[J]. Am J Perinatol, 2015, 30(2):115-122.
[29]
Lynex CN, Carr IM, Leek JP, et al. Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy:parallels with Stiff-Person syndrome and other movement disorders[J]. BMC Neurol, 2004, 4(1):20.
[30]
Zhubi A, Chen Y, Guidotti A, et al. Epigenetic regulation of RELN and GAD1 in the frontal cortex (FC) of autism spectrum disorder (ASD) subjects[J]. Int J Dev Neurosci, 2017. doi:10.1016/j.ijdevneu.2017.02.003.[Epub ahead of print].
[31]
Lerer I, Sagi M, Meiner V, et al. Deletion of the ANKRD15 gene at 9p24.3 causes parent-of-origin-dependent inheritance of familial cerebral palsy[J]. Hum Mol Genet, 2005, 14(24):3911-3920.
[32]
Clohisey SM, Dzhindzhev NS, Ohkura H. Kank is an EB1 interacting protein that localises to muscle-tendon attachment sites in Drosophila[J]. PLoS One, 2014, 9(9):e106112.
[33]
Bouchet BP, Gough RE, Ammon YC, et al. Talin-KANK1 interaction controls the recruitment of cortical microtubule stabilizing complexes to focal adhesions[J]. Elife, 2016, 5:e18124.
[34]
Frazier MN, Davies AK, Voehler M, et al. Molecular basis for the interaction between AP4β4 and its accessory protein, tepsin[J]. Traffic, 2016, 17(4):400-415.
[35]
Verkerk AJ, Schot R, Dumee B, et al. Mutation in the AP4M1 gene provides a model for neuroaxonal injury in cerebral palsy[J]. Am J Hum Genet, 2009, 85(1):40-52.
[36]
Abou JR, Philippe O, Raas-Rothschild A, et al. Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature[J]. Am J Hum Genet, 2011, 88(6):788-795.
[37]
Moreno-De-Luca A, Helmers SL, Mao H, et al. Adaptor protein complex-4(AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability[J]. J Med Genet, 2011, 48(2):141-144.
[38]
Yap CC, Murate M, Kishigami S, et al. Adaptor protein complex-4(AP-4) is expressed in the central nervous system neurons and interacts with glutamate receptor delta2[J]. Mol Cell Neurosci, 2003, 24(2):283-295.
[39]
Matsuda S, Yuzaki M. Polarized sorting of AMPA receptors to the somatodendritic domain is regulated by adaptor protein AP-4[J]. Neurosci Res, 2009, 65(1):1-5.
[40]
Dohare P, Zia MT, Ahmed E, et al. AMPA-kainate receptor inhibition promotes neurologic recovery in premature rabbits with intraventricular hemorrhage[J]. J Neurosci, 2016, 36(11):3363-3377.
[41]
Kruer MC, Jepperson T, Dutta S, et al. Mutations in gamma adducin are associated with inherited cerebral palsy[J]. Ann Neurol, 2013, 74(6):805-814.
[42]
Pei J, Dong R, Yang Y, et al. Association of STAT4 genetic polymorphisms with biliary atresia in Chinese patients[J]. Int J Clin Exp Pathol, 2017, 10(3):3451-3455.
[43]
Parolin Schnekenberg R, Perkins EM, Miller JW, et al. De novo point mutations in patients diagnosed with ataxic cerebral palsy[J]. Brain, 2015, 138(Pt7):1817-1832.
