Mutations of the RTEL1 Helicase in a Hoyeraal-Hreidarsson Syndrome Patient Highlight the Importance of the ARCH Domain

Hum Mutat. 2016 May;37(5):469-72. doi: 10.1002/humu.22966. Epub 2016 Feb 23.

Abstract

The DNA helicase RTEL1 participates in telomere maintenance and genome stability. Biallelic mutations in the RTEL1 gene account for the severe telomere biology disorder characteristic of the Hoyeraal-Hreidarsson syndrome (HH). Here, we report a HH patient (P4) carrying two novel compound heterozygous mutations in RTEL1: a premature stop codon (c.949A>T, p.Lys317*) and an intronic deletion leading to an exon skipping and an in-frame deletion of 25 amino-acids (p.Ile398_Lys422). P4's cells exhibit short and dysfunctional telomeres similarly to other RTEL1-deficient patients. 3D structure predictions indicated that the p.Ile398_Lys422 deletion affects a part of the helicase ARCH domain, which lines the pore formed with the core HD and the iron-sulfur cluster domains and is highly specific of sequences from the eukaryotic XPD family members.

Keywords: ARCH domain; Hoyeraal-Hreidarsson syndrome; RTEL1; Telomere; XPD.

Publication types

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

MeSH terms

  • Child
  • Codon, Terminator
  • DNA Helicases / chemistry*
  • DNA Helicases / genetics*
  • Dyskeratosis Congenita / genetics*
  • Female
  • Fetal Growth Retardation / genetics*
  • Humans
  • Intellectual Disability / genetics*
  • Microcephaly / genetics*
  • Models, Molecular
  • Mutation*
  • Protein Domains
  • Sequence Deletion

Substances

  • Codon, Terminator
  • RTEL1 protein, human
  • DNA Helicases

Supplementary concepts

  • Hoyeraal Hreidarsson syndrome