Primary immunodeficiency with chronic enteropathy and developmental delay in a boy arising from a novel homozygous RIPK1 variant

J Hum Genet. 2019 Sep;64(9):955-960. doi: 10.1038/s10038-019-0631-3. Epub 2019 Jun 18.

Abstract

Identification of genetic causes of primary monogenic immunodeficiencies would strengthen the current understanding of their immunopathology. Pathogenic variants in genes in association with tumor necrosis factor α (TNFα) signaling, including OTULIN, TNFAIP3, RBCK1, and RNF31 cause human congenital autoinflammatory diseases with/without immunodeficiency. RIPK1, encoding a receptor interacting serine/threonine kinase 1, is present in protein complexes mediating signal transduction including TNF receptor 1. Biallelic loss-of-function variants in RIPK1 were recently reported in individuals with primary immunodeficiency with intestinal bowel disease and arthritis. Here, we report a novel homozygous RIPK1 variant in a boy with immunodeficiency and chronic enteropathy. Our patient exhibited severe motor delay and mild intellectual disability, which were previously unknown. The present results are expected to deepen the current understanding of clinical features based on RIPK1 abnormalities.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Developmental Disabilities / genetics*
  • Homozygote*
  • Humans
  • Intestinal Diseases / genetics*
  • Loss of Function Mutation*
  • Male
  • Primary Immunodeficiency Diseases / genetics*
  • Receptor-Interacting Protein Serine-Threonine Kinases / genetics*
  • Signal Transduction / genetics*

Substances

  • RIPK1 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases