title: Mutations of the RTEL1 Helicase in a Hoyeraal-Hreidarsson Syndrome Patient Highlight the Importance of the ARCH Domain.
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.
authors: INSERM UMR 1163, Laboratory of Genome Dynamics in the Immune System, Labellisé Ligue.|Paris Descartes - Sorbonne Paris Cité University, Imagine Institute, Paris, France.
authors: Laurent
authors: L
authors: Jullien
authors: Assistance Publique des Hôpitaux de Paris, Hôpital Bichat, Service de Génétique, Université Paris Diderot, Paris, France.
authors: Caroline
authors: C
authors: Kannengiesser
authors: INSERM UMR 1163, Laboratory of Genome Dynamics in the Immune System, Labellisé Ligue.|Paris Descartes - Sorbonne Paris Cité University, Imagine Institute, Paris, France.
authors: Laetitia
authors: L
authors: Kermasson
authors: Department of Genetics, INSERM UMR 1163, Paris Descartes University-Sorbonne Paris Cité, Imagine Institute, Necker enfants malades Hospital, Paris, France.
authors: Valérie
authors: V
authors: Cormier-Daire
authors: Assistance Publique - Hôpitaux de Paris, Hôpital Robert-Debré, Service d'Hématologie Pédiatrique, Paris, France.
authors: Thierry
authors: T
authors: Leblanc
authors: Institute of Hematology (IUH), INSERM UMR944/CNRS UMR7212, Saint-Louis Hospital and University Paris Diderot, Sorbonne Paris Cité, av Claude, Vellefaux, Paris, France.
authors: Jean
authors: J
authors: Soulier
authors: Telomeres and Cancer Laboratory, Labellisé Ligue, Department UMR3244, Institut Curie, Paris, France.
authors: Arturo
authors: A
authors: Londono-Vallejo
authors: INSERM UMR 1163, Laboratory of Genome Dynamics in the Immune System, Labellisé Ligue.|Paris Descartes - Sorbonne Paris Cité University, Imagine Institute, Paris, France.
authors: Jean-Pierre
authors: JP
authors: de Villartay
authors: IMPMC, Sorbonne Universités, UMR CNRS 7590, UPMC Univ Paris06, Muséum National d'Histoire Naturelle, IRD UMR 206, Paris, France.
authors: Isabelle
authors: I
authors: Callebaut
authors: INSERM UMR 1163, Laboratory of Genome Dynamics in the Immune System, Labellisé Ligue.|Paris Descartes - Sorbonne Paris Cité University, Imagine Institute, Paris, France.
authors: Patrick
authors: P
authors: Revy
mesh_terms: D002648:Child; D018388:Codon, Terminator; D004265:DNA Helicases / Q000737:chemistry* / Q000235:genetics*; D019871:Dyskeratosis Congenita / Q000235:genetics*; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008831:Microcephaly / Q000235:genetics*; D008958:Models, Molecular; D009154:Mutation; D000072417:Protein Domains; D017384:Sequence Deletion
chemical_list: D018388:Codon, Terminator; C532890:RTEL1 protein, human; D004265:DNA Helicases
keywords: ARCH domain; Hoyeraal-Hreidarsson syndrome; RTEL1; Telomere; XPD