Recessive mutation in CD2AP causes focal segmental glomerulosclerosis in humans and mice

Kidney Int. 2019 Jan;95(1):57-61. doi: 10.1016/j.kint.2018.08.014. Epub 2018 Oct 26.

Abstract

Although sequence variants in CD2-associated protein (CD2AP) have been identified in patients with focal segmental glomerulosclerosis (FSGS), definitive proof of causality in human disease is meager. By whole-exome sequencing, we identified a homozygous frame-shift mutation in CD2AP (p.S198fs) in three siblings born of consanguineous parents who developed childhood-onset FSGS and end stage renal disease. When the same frameshift mutation was introduced in mice by gene editing, the mice developed FSGS and kidney failure. These results provide conclusive evidence that homozygous mutation of CD2AP causes FSGS in humans.

Keywords: CD2AP; CRISPR/Cas9; FSGS; gene editing.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Consanguinity
  • Cytoskeletal Proteins / genetics*
  • Disease Models, Animal
  • Disease Progression
  • Exome Sequencing
  • Female
  • Frameshift Mutation
  • Gene Editing
  • Gene Knock-In Techniques
  • Glomerulosclerosis, Focal Segmental / genetics*
  • Glomerulosclerosis, Focal Segmental / pathology
  • Homozygote
  • Humans
  • Kidney Failure, Chronic / genetics
  • Kidney Failure, Chronic / pathology*
  • Male
  • Mice
  • Mice, Transgenic
  • Pedigree

Substances

  • Adaptor Proteins, Signal Transducing
  • CD2-associated protein
  • Cytoskeletal Proteins

Grants and funding