Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD)

Author:

Chakraborty Pranesh K.1,Schmitz-Abe Klaus2,Kennedy Erin K.3,Mamady Hapsatou1,Naas Turaya1,Durie Danielle1,Campagna Dean R.4,Lau Ashley4,Sendamarai Anoop K.4,Wiseman Daniel H.5,May Alison6,Jolles Stephen7,Connor Philip8,Powell Colin9,Heeney Matthew M.10,Giardina Patricia-Jane11,Klaassen Robert J.12,Kannengiesser Caroline13,Thuret Isabelle14,Thompson Alexis A.15,Marques Laura16,Hughes Stephen17,Bonney Denise K.5,Bottomley Sylvia S.18,Wynn Robert F.5,Laxer Ronald M.19,Minniti Caterina P.20,Moppett John21,Bordon Victoria22,Geraghty Michael12,Joyce Paul B. M.23,Markianos Kyriacos2,Rudner Adam D.3,Holcik Martin24,Fleming Mark D.4

Affiliation:

1. Newborn Screening Ontario, Department of Pediatrics, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada;

2. Division of Genetics and Genomics, Department of Medicine, Boston Children's Hospital, Boston, MA;

3. Ottawa Institute of Systems Biology and BMI, University of Ottawa, Ottawa, ON, Canada;

4. Department of Pathology, Boston Children's Hospital, Boston, MA;

5. Department of Haematology, Royal Manchester Children’s Hospital, Manchester, United Kingdom;

6. Department of Haematology, Cardiff University School of Medicine, Cardiff, United Kingdom;

7. Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, United Kingdom;

8. Department of Paediatrics, Children’s Hospital for Wales, Cardiff, United Kingdom;

9. Department of Child Health, Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Children’s Hospital for Wales, Cardiff, United Kingdom;

10. Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA;

11. Division of Hematology-Oncology, Children’s Cancer and Blood Foundation Laboratories, Weill Cornell Medical College, New York, NY;

12. Department of Pediatrics, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada;

13. INSERM UMR773, Université Paris Diderot, Assistance Publique des Hospitaux de Paris, Département de Génétique, Hôpital Xavier Bichat, Paris, France;

14. Department of Pediatric Hematology, Hôpital de la Timone, Marseille, France;

15. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children’s Hospital, Chicago, IL;

16. Paediatric Department, Infectious Diseases and Immunodeficiencies Unit, Centro Hospitalar do Porto, Porto, Portugal;

17. Department of Immunology, Royal Manchester Children’s Hospital, Manchester, United Kingdom;

18. Department of Medicine, Hematology-Oncology Section, University of Oklahoma College of Medicine, Oklahoma City, OK;

19. Department of Paediatrics and Medicine, The Hospital for Sick Children, University of Toronto, ON, Canada;

20. Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;

21. Bristol Children's Hospital, Bristol, United Kingdom;

22. Department of Pediatric Hemato-Oncology and Stem Cells Transplant, Universitair Ziekenhuis Ghent, Belgium;

23. Department of Chemistry and Biochemistry and Center for Structural and Functional Genomics, Concordia University, Montreal, QC, Canada; and

24. Molecular Biomedicine Program, Children's Hospital of Eastern Ontario Research Institute, Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada

Abstract

Key PointsSIFD is a syndromic form of congenital sideroblastic anemia associated with immunodeficiency, periodic fevers, and developmental delay. SIFD is due to partial loss-of-function mutations in the CCA-adding enzyme TRNT1.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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