title: Mutations in CDCA7 and HELLS cause immunodeficiency-centromeric instability-facial anomalies syndrome.
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.
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden 2333ZA, The Netherlands.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Thijssen
authors.affiliation: Division of Epigenomics and Development, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Ito
authors.affiliation: CNRS UMR7216, Epigenetics and Cell Fate, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris, France.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Grillo
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden 2333ZA, The Netherlands.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: CNRS UMR7216, Epigenetics and Cell Fate, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Velasco
authors.affiliation: Division of Epigenomics and Development, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Nitta
authors.affiliation: Division of Epigenomics and Development, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Unoki
authors.affiliation: Division of Bioinformatics, Department of Multi-scale Research Center for Medical Science, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Yoshihara
authors.affiliation: Division of Bioinformatics, Department of Multi-scale Research Center for Medical Science, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Mikita
authors.initials: M
authors.lastname: Suyama
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden 2333ZA, The Netherlands.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden 2333ZA, The Netherlands.
authors.forename: Richard J L F
authors.initials: RJ
authors.lastname: Lemmers
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden 2333ZA, The Netherlands.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: de Greef
authors.affiliation: 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.
authors.forename: Andrew
authors.initials: A
authors.lastname: Gennery
authors.affiliation: Division of Pediatrics and Pediatric Rheumatology, G. Gaslini Scientific Institute, Genova 16147, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Picco
authors.affiliation: 1] Institute of Medical Molecular Genetics, University of Zurich, Schlieren 8952, Switzerland [2] Department of Biology, ETH Zurich, Zurich 8093, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kloeckener-Gruissem
authors.affiliation: Department of Oncology, University Children's Hospital, Zurich 8032, Switzerland.
authors.forename: Tayfun
authors.initials: T
authors.lastname: Güngör
authors.affiliation: Department of Pediatric Immunology and Allergy, Necmettin Erbakan University, Meram Medical Faculty, Konya 42080, Turkey.
authors.forename: Ismail
authors.initials: I
authors.lastname: Reisli
authors.affiliation: 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.
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.affiliation: Centre de Référence Déficits Immunitaires Héréditaires, Institut d'Hématologie et d'Oncologie Pédiatrique, CHU de Lyon, 69008 Lyon, France.
authors.forename: Kamila
authors.initials: K
authors.lastname: Kebaili
authors.affiliation: Service d'hépato-gastro-entérologie et nutrition, endocrinologie et néphrologie pédiatriques, Hôpital de la Timone, CHU Marseille, 13385 Marseille, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Roquelaure
authors.affiliation: Department of Pediatric Hematology and Oncology, Shikoku Medical Center for Children and adults, Kagawa 765-8507, Japan.
authors.forename: Tsuyako
authors.initials: T
authors.lastname: Iwai
authors.affiliation: Department of Pediatrics, Ooida Hospital, Kochi 788-0001, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kondo
authors.affiliation: Department of Epigenetic Medicine, Faculty of Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Kubota
authors.affiliation: Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Center, Leiden 2333ZA, The Netherlands.
authors.forename: Monique M
authors.initials: MM
authors.lastname: van Ostaijen-Ten Dam
authors.affiliation: Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Center, Leiden 2333ZA, The Netherlands.
authors.forename: Maarten J D
authors.initials: MJ
authors.lastname: van Tol
authors.affiliation: Department of Pediatric Infectious Diseases and Immunology, Radboud University Nijmegen Medical Center, Nijmegen 6500HC, The Netherlands.
authors.forename: Corry
authors.initials: C
authors.lastname: Weemaes
authors.affiliation: CNRS UMR7216, Epigenetics and Cell Fate, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Francastel
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden 2333ZA, The Netherlands.
authors.forename: Silvère M
authors.initials: SM
authors.lastname: van der Maarel
authors.affiliation: Division of Epigenomics and Development, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004265:DNA Helicases / Q000235:genetics*; D005145:Face / Q000002:abnormalities*; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D007223:Infant; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics*; D000081207:Primary Immunodeficiency Diseases; D055815:Young Adult
chemical_list: C445325:CDCA7 protein, human; D009687:Nuclear Proteins; D004265:DNA Helicases; C412063:HELLS protein, human