Long‐term assessment of haematological recovery following somatic genetic rescue in a MYSM1‐deficient patient: Implications for in vivo gene therapy

Sophie de Tocqueville (1) , Emmanuel Martin (1) , Quentin Riller (1) , Laëtitia Kermasson (1) , Benoit France (1) , Aude Magérus (1) , Frédéric Rieux-Laucat (1) , François Delhommeau (2, 3) , Pierre Hirsch (2, 3) , Aurore Touzart (4, 5) , Aude Echalier (6) , Alain Fischer (4, 1) , Despina Moshous (1, 4) , Patrick Revy (1)

1 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
2 CRSA - Centre de Recherche Saint-Antoine
3 CHU Saint-Antoine [AP-HP]
4 Hôpital Necker - Enfants Malades [AP-HP]
5 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
6 University of Leicester

Summary MYSM1 deficiency causes inherited bone marrow failure syndrome (IBMFS). We have previously identified an IBMFS patient with a homozygous pathogenic variant in MYSM1 who recovered from cytopenia due to spontaneous correction of one MYSM1 variant in the haematopoietic compartment, an event called somatic genetic rescue (SGR). The study of the genetic and biological aspects of the patient's haematopoietic/lymphopoietic system over a decade after SGR shows that one genetically corrected haematopoietic stem cell (HSC) can restore a healthy and stable haematopoietic system. This supports in vivo gene correction of HSCs as a promising treatment for IBMFS, including MYSM1 deficiency.

Keywords: MYSM1; bone marrow failure; haematopoiesis; natural gene therapy; somatic genetic rescue

Domains: Life Sciences [q-bio]

Sophie de Tocqueville, Emmanuel Martin, Quentin Riller, Laëtitia Kermasson, Benoit France, et al.. Long‐term assessment of haematological recovery following somatic genetic rescue in a MYSM1‐deficient patient: Implications for in vivo gene therapy. British Journal of Haematology, 2024, Online ahead of print. ⟨10.1111/bjh.19744⟩. ⟨hal-04727273⟩