Novel truncating PPM1D mutation in a patient with intellectual disability

Eur J Med Genet. 2019 Jan;62(1):70-72. doi: 10.1016/j.ejmg.2018.05.006. Epub 2018 May 11.

Abstract

Truncating mutations in the last and penultimate exons of the PPM1D gene were recently described as a cause for mild to severe intellectual disability in fourteen patients. Feeding difficulties, periods of fever and vomiting as well as a high pain threshold were described as additional characteristic features and the disorder was subsequently termed "intellectual developmental disorder with gastrointestinal difficulties and high pain threshold (IDDGIP)" in the OMIM database (MIM # 617450). Here we report on an additional patient carrying a novel de novo truncating mutation NM_003620.3: c.1535del, p.(Asn512Ilefs*2) in the last exon of PPM1D. While the patient showed features overlapping with the reported phenotype, such as a short stature and small hands and feet, he also presented with additional features like cleft lip and palate and an aberrant right subclavian artery. Notably, the patient did not have any gastrointestinal difficulties or periods of fever, indicating variability of the phenotype of patients with PPM1D mutations.

Keywords: Cleft lip and palate; High pain threshold; Intellectual disability; PPM1D; Short stature.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Child
  • Gastrointestinal Diseases / genetics*
  • Gastrointestinal Diseases / pathology
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Male
  • Mutation*
  • Pain Threshold*
  • Phenotype*
  • Protein Phosphatase 2C / genetics*
  • Syndrome

Substances

  • PPM1D protein, human
  • Protein Phosphatase 2C