2. Academic Validation
  3. Mutations in CDCA7 and HELLS cause immunodeficiency-centromeric instability-facial anomalies syndrome

Mutations in CDCA7 and HELLS cause immunodeficiency-centromeric instability-facial anomalies syndrome

  • Nat Commun. 2015 Jul 28;6:7870. doi: 10.1038/ncomms8870.
Peter E Thijssen 1,  Yuya Ito 2,  Giacomo Grillo 3,  Jun Wang 1,  Guillaume Velasco 3,  Hirohisa Nitta 2,  Motoko Unoki 2,  Minako Yoshihara 4,  Mikita Suyama 4,  Yu Sun 1,  Richard J L F Lemmers 1,  Jessica C de Greef 1,  Andrew Gennery 5,  Paolo Picco 6,  Barbara Kloeckener-Gruissem 7,  Tayfun Güngör 8,  Ismail Reisli 9,  Capucine Picard 10,  Kamila Kebaili 11,  Bertrand Roquelaure 12,  Tsuyako Iwai 13,  Ikuko Kondo 14,  Takeo Kubota 15,  Monique M van Ostaijen-Ten Dam 16,  Maarten J D van Tol 16,  Corry Weemaes 17,  Claire Francastel 3,  Silvère M van der Maarel 1,  Hiroyuki Sasaki 2
Affiliations

Affiliations

  • 1 Department of Human Genetics, Leiden University Medical Center, Leiden 2333ZA, The Netherlands.
  • 2 Division of Epigenomics and Development, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
  • 3 CNRS UMR7216, Epigenetics and Cell Fate, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris, France.
  • 4 Division of Bioinformatics, Department of Multi-scale Research Center for Medical Science, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
  • 5 1] Department of Paediatric Immunology, Newcastle Upon Tyne Hospital, NHS Foundation Trust, Newcastle Upon Tyne, UK [2] Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne NE1 4LP, UK.
  • 6 Division of Pediatrics and Pediatric Rheumatology, G. Gaslini Scientific Institute, Genova 16147, Italy.
  • 7 1] Institute of Medical Molecular Genetics, University of Zurich, Schlieren 8952, Switzerland [2] Department of Biology, ETH Zurich, Zurich 8093, Switzerland.
  • 8 Department of Oncology, University Children's Hospital, Zurich 8032, Switzerland.
  • 9 Department of Pediatric Immunology and Allergy, Necmettin Erbakan University, Meram Medical Faculty, Konya 42080, Turkey.
  • 10 1] Centre de Référence Déficits Immunitaires Héréditaires, AP-HP, 75743 Paris, France [2] Centre d'Etude des Déficits Immunitaires, Hôpital Universitaire Necker-Enfants Malades, AP-HP, 75743 Paris, France [3] Laboratoire de Génétique Humaine des Maladies Infectieuses, Inserm, 75743, Paris, France [4] Université Paris Descartes, Institut Imagine, Sorbonne Paris, 75743 Paris, France [5] Unité d'immunologie et d'hématologie pédiatrique, Hôpital Necker-Enfants Malades, 75743, Paris, France [6] Inserm UMR 768, 75015 Paris, France.
  • 11 Centre de Référence Déficits Immunitaires Héréditaires, Institut d'Hématologie et d'Oncologie Pédiatrique, CHU de Lyon, 69008 Lyon, France.
  • 12 Service d'hépato-gastro-entérologie et nutrition, endocrinologie et néphrologie pédiatriques, Hôpital de la Timone, CHU Marseille, 13385 Marseille, France.
  • 13 Department of Pediatric Hematology and Oncology, Shikoku Medical Center for Children and adults, Kagawa 765-8507, Japan.
  • 14 Department of Pediatrics, Ooida Hospital, Kochi 788-0001, Japan.
  • 15 Department of Epigenetic Medicine, Faculty of Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898, Japan.
  • 16 Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Center, Leiden 2333ZA, The Netherlands.
  • 17 Department of Pediatric Infectious Diseases and Immunology, Radboud University Nijmegen Medical Center, Nijmegen 6500HC, The Netherlands.
PMID: 26216346 DOI: 10.1038/ncomms8870
Abstract

The life-threatening Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome is a genetically heterogeneous autosomal recessive disorder. Twenty percent of patients cannot be explained by mutations in the known ICF genes DNA Methyltransferase 3B or zinc-finger and BTB domain containing 24. Here we report mutations in the cell division cycle associated 7 and the helicase, lymphoid-specific genes in 10 unexplained ICF cases. Our data highlight the genetic heterogeneity of ICF syndrome; however, they provide evidence that all genes act in common or converging pathways leading to the ICF phenotype.

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