Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms

Author:

Tesi Bianca1234,Davidsson Josef56,Voss Matthias1,Rahikkala Elisa78,Holmes Tim D.19,Chiang Samuel C. C.1,Komulainen-Ebrahim Jonna710,Gorcenco Sorina11,Rundberg Nilsson Alexandra5,Ripperger Tim12,Kokkonen Hannaleena13,Bryder David5,Fioretos Thoas14,Henter Jan-Inge2,Möttönen Merja710,Niinimäki Riitta710,Nilsson Lars15,Pronk Cornelis Jan56,Puschmann Andreas11,Qian Hong1,Uusimaa Johanna710,Moilanen Jukka78,Tedgård Ulf6,Cammenga Jörg51617,Bryceson Yenan T.19

Affiliation:

1. Centre for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden;

2. Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden;

3. Division of Pediatrics, and

4. Clinical Genetics Unit, Department of Molecular Medicine and Surgery, and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden;

5. Division of Molecular Hematology, Institution for Laboratory Medicine, Lund University, Lund, Sweden;

6. Department of Pediatric Oncology and Hematology, Skåne University Hospital, Lund, Sweden;

7. PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu, Oulu, Finland;

8. Department of Clinical Genetics, Oulu University Hospital, Oulu, Finland;

9. Broegelmann Research Laboratory, Department of Clinical Sciences, University of Bergen, Bergen, Norway;

10. Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland;

11. Department of Neurology, Lund University, Lund, Sweden;

12. Department of Human Genetics, Hannover Medical School, Hannover, Germany;

13. Department of Clinical Chemistry, Oulu University Hospital, Oulu, Finland;

14. Department of Clinical Genetics, Lund University, Lund, Sweden;

15. Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden;

16. Department of Hematology, Linköping University Hospital, Linköping, Sweden; and

17. Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden

Abstract

Key Points Autosomal-dominant SAMD9L gain-of-function mutations predispose to myeloid malignancies involving chromosome 7 aberrations. Hematopoietic reversions frequently occur postnatally and are associated with milder disease manifestations.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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