Impact of germline CTC1 alterations on telomere length in acquired bone marrow failure

Br J Haematol. 2019 Jun;185(5):935-939. doi: 10.1111/bjh.15862. Epub 2019 Mar 19.

Abstract

Compound heterozygous germline mutations in CTC1 gene have been found in patients with atypical dyskeratosis congenita (DC), whereas heterozygous carriers are unaffected. Through screening of a large cohort of adult patients with acquired bone marrow failure syndromes, in addition to a DC case, we have also found extremely rare or novel heterozygous deleterious germline variants of CTC1 in patients with aplastic anaemia (AA; n = 5), paroxysmal nocturnal haemoglobinuria (PNH; n = 3) and myelodysplastic syndrome (MDS; n = 2). A compound heterozygous case of AA showed clonal evolution. Our results suggest that some of the inherited CTC1 variants may represent predisposition factors for acquired bone marrow failure.

Keywords: CTC1; bone marrow failure; germline variant; heterozygous; telomere length.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Marrow Failure Disorders / genetics*
  • Bone Marrow Failure Disorders / metabolism
  • Bone Marrow Failure Disorders / pathology
  • Female
  • Germ-Line Mutation*
  • Humans
  • Male
  • Middle Aged
  • Telomere / genetics*
  • Telomere / metabolism
  • Telomere / pathology
  • Telomere-Binding Proteins / genetics*
  • Telomere-Binding Proteins / metabolism

Substances

  • Ctc1 protein, human
  • Telomere-Binding Proteins