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Mutations of the RTEL1 Helicase in a Hoyeraal‐Hreidarsson Syndrome Patient Highlight the Importance of the ARCH Domain
Author(s) -
Jullien Laurent,
Kannengiesser Caroline,
Kermasson Laetitia,
CormierDaire Valérie,
Leblanc Thierry,
Soulier Jean,
LondonoVallejo Arturo,
Villartay JeanPierre,
Callebaut Isabelle,
Revy Patrick
Publication year - 2016
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22966
Subject(s) - biology , helicase , telomere , genetics , mutation , exon , stop codon , gene , rna
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.