TCIRG1-associated congenital neutropenia

Hum Mutat. 2014 Jul;35(7):824-7. doi: 10.1002/humu.22563. Epub 2014 May 21.

Abstract

Severe congenital neutropenia (SCN) is a rare hematopoietic disorder, with estimated incidence of 1 in 200,000 individuals of European descent, many cases of which are inherited in an autosomal dominant pattern. Despite the fact that several causal genes have been identified, the genetic basis for >30% of cases remains unknown. We report a five-generation family segregating a novel single nucleotide variant (SNV) in TCIRG1. There is perfect cosegregation of the SNV with congenital neutropenia in this family; all 11 affected, but none of the unaffected, individuals carry this novel SNV. Western blot analysis show reduced levels of TCIRG1 protein in affected individuals, compared to healthy controls. Two unrelated patients with SCN, identified by independent investigators, are heterozygous for different, rare, highly conserved, coding variants in TCIRG1.

Keywords: SCN; TCIRG1; V-ATPase; congenital neutropenia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Congenital Bone Marrow Failure Syndromes
  • DNA Mutational Analysis
  • Heterozygote
  • Humans
  • Mutation
  • Neutropenia / congenital*
  • Neutropenia / diagnosis
  • Neutropenia / genetics
  • Neutropenia / metabolism
  • Pedigree
  • Vacuolar Proton-Translocating ATPases / genetics*
  • Vacuolar Proton-Translocating ATPases / metabolism

Substances

  • TCIRG1 protein, human
  • Vacuolar Proton-Translocating ATPases

Supplementary concepts

  • Neutropenia, Severe Congenital, Autosomal Recessive 3