Human ITCH E3 ubiquitin ligase deficiency causes syndromic multisystem autoimmune disease

Am J Hum Genet. 2010 Mar 12;86(3):447-53. doi: 10.1016/j.ajhg.2010.01.028. Epub 2010 Feb 18.

Abstract

Ubiquitin ligases play an important role in the regulation of the immune system. Absence of Itch E3 ubiquitin ligase in mice has been shown to cause severe autoimmune disease. Using autozygosity mapping in a large Amish kindred, we identified a linkage region on chromosome 20 and selected candidate genes for screening. We describe, in ten patients, identification of a mutation resulting in truncation of ITCH. These patients represent the first reported human phenotype associated with ITCH deficiency. These patients not only have multisystem autoimmune disease but also display morphologic and developmental abnormalities. This disorder underscores the importance of ITCH ubiquitin ligase in many cellular processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Autoimmune Diseases / enzymology*
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / pathology
  • Base Sequence
  • Child
  • Child, Preschool
  • Chromosome Mapping
  • Chromosomes, Human, Pair 20 / genetics
  • Consanguinity
  • DNA / genetics
  • Developmental Disabilities / enzymology
  • Developmental Disabilities / genetics
  • Ethnicity / genetics
  • Female
  • Frameshift Mutation*
  • Homozygote
  • Humans
  • Infant
  • Male
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Pedigree
  • Phenotype
  • Repressor Proteins / deficiency*
  • Repressor Proteins / genetics*
  • Syndrome
  • Ubiquitin-Protein Ligases / deficiency*
  • Ubiquitin-Protein Ligases / genetics*
  • United States
  • Young Adult

Substances

  • Repressor Proteins
  • DNA
  • ITCH protein, human
  • Ubiquitin-Protein Ligases