Mutations in CDCA7 and HELLS cause immunodeficiency-centromeric instability-facial anomalies syndrome PMID: 26216346

RQC and Longevity Regulation

2026-09-03

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

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.

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.