A Novel Missense Variant in the Gene PPP2R5D Causes a Rare Neurodevelopmental Disorder with Increased Phenotype

Biomed Res Int. 2021 Feb 11:2021:6661860. doi: 10.1155/2021/6661860. eCollection 2021.


PPP2R5D-related neurodevelopmental disorder, which is mainly caused by de novo missense variants in the PPP2R5D gene, is a rare autosomal dominant genetic disorder with about 100 patients and a total of thirteen pathogenic variants known to exist globally so far. Here, we present a 24-month-old Chinese boy with developmental delay and other common clinical characteristics of PPP2R5D-related neurodevelopmental disorder including hypotonia, macrocephaly, intellectual disability, speech impairment, and behavioral abnormality. Trio-whole exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variant. The pathogenicity of the variant was evaluated using bioinformatics tools. We identified a novel pathogenic variant in the PPP2R5D gene (c.620G>T, p.Trp207Leu). The variant is located in the variant hotspot region of this gene and is predicted to cause PPP2R5D protein dysfunction due to an increase in local hydrophobicity and unstable three-dimensional structure. We report a novel pathogenic variant of PPP2R5D associated with PPP2R5D-related neurodevelopmental disorder from a Chinese family. Our findings expanded the phenotypic and mutational spectrum of PPP2R5D-related neurodevelopmental disorder.

Publication types

  • Clinical Trial
  • Retracted Publication

MeSH terms

  • Amino Acid Substitution
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Intellectual Disability / genetics*
  • Male
  • Mutation, Missense*
  • Neurodevelopmental Disorders / genetics*
  • Pedigree*
  • Phenotype*
  • Protein Phosphatase 2 / genetics*


  • PPP2R5D protein, human
  • Protein Phosphatase 2