Haematopoietic Stem Cell Transplantation for DNA Ligase 1 Deficiency
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LETTER TO EDITOR
Haematopoietic Stem Cell Transplantation for DNA Ligase 1 Deficiency Juliana M. F. Silva 1 & Alison Jones 2 & Keith Sibson 3 & Shahnaz Bibi 4 & Penny Jeggo 5 & Lisa Woodbine 5 & Gulrukh Ahsan 2 & Kimberly C. Gilmour 2 & Kanchan Rao 1 & Robert Chiesa 1 & Giovanna Lucchini 1 & Paul Veys 1 & Austen Worth 1,6 & Persis J. Amrolia 1 Received: 17 September 2019 / Accepted: 16 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abbreviations ASQ Ages and stages questionnaire GVHD Graft versus host disease HLA Human leukocyte antigen HSCT Haematopoietic stem cell transplant LIG1 DNA ligase 1 gene mAbs Monoclonal antibodies NK Natural killer PHA Phytohaemagglutinin RSV Respiratory Syncytial virus TRECs T cell receptor excision circles
To the Editor: DNA ligase 1 is critical for DNA single-strand break repair and DNA replication [1]. Mutations in DNA ligase 1 gene (LIG1) have been previously described to be associated with in vitro hypersensitivity to DNA-damaging
agents and impaired Okazaki fragment joining, and clinically patients with LIG1 mutations have a combined immunodeficiency [2]. Five patients have been previously identified (including three patients described here) with early-onset hypogammaglobulinemia, lymphopenia with reduced αβ T cell numbers, but raised γδ T cells and macrocytic red blood cells not associated with B12 or folate deficiency [3]. One previous patient has been reported with DNA ligase 1 deficiency with combined immunodeficiency, growth retardation and sun sensitivity who died of lymphoma at 19 years of age [4]. We report two brothers with pathological mutations in LIG1, who presented in infancy with severe combined immunodeficiency and transfusion dependent anaemia who underwent haematopoietic stem cell transplantation at our institution. Since LIG1 is ubiquitously expressed, minimal intensity conditioning was utilised to reduce DNA damage and hence toxicity to the nonhaematopoietic tissues.
Austen Worth and Persis J. Amrolia share the last co-authorship as they contributed equally to the manuscript. Capsule Summary: DNA ligase I deficiency is a novel cause of severe combined immunodeficiency and should be considered in the presence of earlyonset immunodeficiency and macrocytic anaemia. We describe the outcomes of two siblings affected by DNA ligase I deficiency who underwent haematopoietic stem cell transplantation. * Persis J. Amrolia [email protected]
4
Regional Molecular Genetics Laboratory, Great Ormond Street Hospital NHS Trust, London, UK
1
Department of Bone Marrow Transplantation, Great Ormond Street Hospital for Children NHS Trust, London, UK
5
Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN19RQ, UK
2
Department of Immunology, Camelia Botnar Laboratories, Great Ormond Street Hospital NHS Trust, London, UK
6
Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
3
Department of Haematology, Great Ormond Street Hospital NHS Trust,
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