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

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