Chinese Journal of Child Health Care ›› 2022, Vol. 30 ›› Issue (7): 809-812.DOI: 10.11852/zgetbjzz2021-1909

• Case Report • Previous Articles    

Case report and literature review on PPP2R1A gene mutation-associated intellectual disability, microcephalus and corpus callosum agenesis

LI Si-xiu, LIU Ping, DENG Jia, CHEN Jia-lei, MAO Dan-dan, HU Wen-guang   

  1. Department of Pediatric Neurology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731, China
  • Received:2021-12-24 Revised:2022-03-03 Online:2022-07-10 Published:2022-07-25
  • Contact: HU Wen-guang, E-mail:


李思秀, 刘平, 邓佳, 陈嘉蕾, 毛丹丹, 胡文广   

  1. 电子科技大学医学院附属妇女儿童医院·成都市妇女儿童中心医院儿童神经内科,成都 611731
  • 通讯作者: 胡文广,
  • 作者简介:李思秀(1982-),女,副主任医师,博士学位,主要从事儿童神经系统疾病及神经发育性疾病的诊治。
  • 基金资助:
    成都市高水平临床重点专科建设项目; 成都市医学科研课题(2019018)

Abstract: Objective To summarize the clinical features and genotypic-phenotypic correlation of PPP2R1A gene variation, so as to provide reference for clinical diagnosis. Methods The medical record of the child with PPP2R1A gene variation diagnosed in July 2021 was retrospectively analyzed. The relevant studies of PPP2R1A gene variation were retrieved. Results The case was a 2-year-old boy manifested with intellectual disability, developmental delay, microcephalus, long face, hypotonia, and corpus callosum agenesis. The whole exome-sequencing test identified a de novo heterozygous variation p.R258H in the PPP2R1A gene. So far, there has been no report of PPP2R1A variation on Chinese journals, but a total of 37 cases have been reported worldwide. All variations of cases were de novo missense mutations (a total of 17 single nucleotide variants), of which p.R182W and p.M180T were the most common sites. The PPP2R1A-related disorder had at least two distinguishable phenotypic subgroups. Common features included moderate to severe intellectual disability (91.2%), developmental delay (78.9%) and hypotonia (86.8%). The least severely affected subgroup encompassed variants in p.F141I, p.T178N/S, and p.M180T/V/K/R, characterized with macrocephaly, absence of seizures. The severely affected subgroup consisted of variants in p.P179L, p.R182W, p.R183W/Q, p.S219L, p.V220M, and p.R258S, characterized with microcephaly, a long face, seizures and corpus callosum hypoplasia. Conclusions The clinical feature of patients with PPP2R1A gene variations is mainly moderate to severe intellectual disability/developmental delay, most co-morbid with hypotonia, macrocephaly or microcephaly, corpus callosum hypoplasia, and abnormal facial shape. There is a certain correlation between genotype and phenotype.

Key words: PPP2R1A gene, intellectual disability, microcephalus, corpus callosum agenesis, gene mutation

摘要: 目的 总结PPP2R1A基因变异的临床特征,探讨基因表型关系。方法 回顾性分析1例2021年7月确诊的PPP2R1A基因变异患儿临床资料,并复习相关文献。结果 2岁男性患儿,临床特征为智力障碍、发育迟缓、小头畸形、长脸、四肢肌张力低下和胼胝体缺如。全外显子测序发现PPP2R1A基因R258H新生错义变异。目前无中文文献报道,全球检索到4篇英文文献37例病例。所有变异均为新生错义变异(共17个单核苷酸变异),其中以p.R182W和p.M180T为热点变异。具有至少两个临床表型,共同临床特征为中重度智力障碍(91.2%),发育迟缓(78.9%),肌张力低下(86.8%),轻症为p.F141I、p.T178N/S和p.M180T/V/K/R变异伴巨头畸形,没有痫性发作;重症为p.P179L、p.R182W、p.R183W/Q、p.S219L、p.V220M和p.R258S/H变异伴小头畸形、长脸、痫性发作和胼胝体发育不全。结论 PPP2R1A基因变异以不同程度智力障碍/发育迟缓合并肌张力低下为主要特征,巨头或小头畸形伴胼胝体发育不全、面部畸形等。基因型与表型存在一定相关性。

关键词: PPP2R1A基因, 智力障碍, 小头畸形, 胼胝体缺如, 基因变异

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