The molecular genetics of the telomere biology disorders

RNA Biol. 2016 Aug 2;13(8):696-706. doi: 10.1080/15476286.2015.1094596. Epub 2015 Sep 23.


The importance of telomere function for human health is exemplified by a collection of Mendelian disorders referred to as the telomere biology disorders (TBDs), telomeropathies, or syndromes of telomere shortening. Collectively, the TBDs cover a spectrum of conditions from multisystem disease presenting in infancy to isolated disease presentations in adulthood, most notably idiopathic pulmonary fibrosis. Eleven genes have been found mutated in the TBDs to date, each of which is linked to some aspect of telomere maintenance. This review summarizes the molecular defects that result from mutations in these genes, highlighting recent advances, including the addition of PARN to the TBD gene family and the discovery of heterozygous mutations in RTEL1 as a cause of familial pulmonary fibrosis.

Keywords: PARN; RTEL1; TERC; TERT; dyskeratosis congenita; hTR; idiopathic pulmonary fibrosis; telomerase; telomere; telomeropathy.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA Replication
  • Dyskeratosis Congenita / genetics
  • Dyskeratosis Congenita / metabolism
  • Enzyme Activation / genetics
  • Exoribonucleases / genetics
  • Exoribonucleases / metabolism
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genomic Instability
  • Humans
  • Mutation
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Transport
  • Syndrome
  • Telomerase / genetics
  • Telomerase / metabolism
  • Telomere / genetics*
  • Telomere / metabolism*
  • Telomere Shortening*


  • Telomerase
  • Exoribonucleases
  • poly(A)-specific ribonuclease