# Unmanipulated bone marrow infusion without conditioning can rescue RECQL4−/− severe combined immunodeficiency **Authors:** Alexandra E. Grier, Marita Bosticardo, Francesca Pala, Ottavia M. Delmonte, Kayla Amini, Eduardo Anaya, Neil Romberg, Susan E. McClory, Nancy J. Bunin, Manar Abdalgani, Luigi D. Notarangelo, Jennifer Heimall PMC · DOI: 10.70962/jhi.20250169 · 2026-03-06 ## TL;DR This paper shows that bone marrow infusion without conditioning can treat severe immunodeficiency caused by RECQL4 mutations. ## Contribution Demonstrates successful treatment of RECQL4−/− SCID using unmanipulated bone marrow infusion without conditioning. ## Key findings - RECQL4−/− SCID can be rescued with unconditioned bone marrow infusion. - T cell defects in RECQL4−/− SCID are intrinsic and transplantable. - DNA repair defects cause radiosensitivity, limiting conditioning options. ## Abstract Mutations in DNA helicase RECQL4 can cause immunodeficiency, including SCID. The T cell defects are intrinsic to the hematopoietic system and amenable to hematopoietic stem cell transplant. Radiosensitivity due to DNA-repair defects limits conditioning regimen options. Mutations in DNA helicase RECQL4 can cause immunodeficiency, including SCID. The T cell defects are intrinsic to the hematopoietic system and amenable to hematopoietic stem cell transplant. Radiosensitivity due to DNA repair defects limits conditioning regimen options. ## Linked entities - **Genes:** RECQL4 (RecQ like helicase 4) [NCBI Gene 9401] - **Diseases:** SCID (MONDO:0015974) ## Full-text entities - **Genes:** PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, PTCRA (pre T cell antigen receptor alpha) [NCBI Gene 171558] {aka IMD126, PT-ALPHA, PTA}, RAG1 (recombination activating 1) [NCBI Gene 5896] {aka RAG-1, RNF74}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, RAG2 (recombination activating 2) [NCBI Gene 5897] {aka RAG-2}, DLL4 (delta like canonical Notch ligand 4) [NCBI Gene 54567] {aka AOS6, delta4, hdelta2}, CD34 (CD34 molecule) [NCBI Gene 947], TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, AK2 (adenylate kinase 2) [NCBI Gene 204] {aka ADK2}, RECQL4 (RecQ like helicase 4) [NCBI Gene 9401] {aka RECQ4}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, KIT (KIT proto-oncogene, receptor tyrosine kinase) [NCBI Gene 3815] {aka C-Kit, CD117, MASTC, PBT, SCFR}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, IL2RG (interleukin 2 receptor subunit gamma) [NCBI Gene 3561] {aka CD132, CIDX, IL-2RG, IMD4, P64, SCIDX} - **Diseases:** fractures (MESH:D050723), congenital anomalies (MESH:D000013), Pneumocystis jirovecii pneumonia (MESH:D011020), growth restriction (MESH:D005317), RTS (MESH:D011038), graft-versus-host disease (MESH:D006086), lymphopenia (MESH:D008231), cancer (MESH:D009369), diarrhea (MESH:D003967), respiratory insufficiency (MESH:D012131), sinopulmonary infections (MESH:C536718), skeletal abnormalities (MESH:D009139), varicella zoster virus infection (MESH:D000073618), hypogammaglobulinemia (MESH:D000361), NK cell deficiency (MESH:D000077428), SCID (MESH:D053632), bone marrow failure (MESH:D000080983), cutaneous granuloma formation (MESH:D058426), craniosynostosis (MESH:D003398), herpesvirus infections (MESH:D006566), sensorineural hearing loss (MESH:D006319), hematopoietic defect (MESH:D019337), immunodeficiency (MESH:D007153), limb anomalies (MESH:C537769), T cell deficiency (MESH:D016399), RAPADILINO syndrome (MESH:C535288), Immune Deficiency (MESH:D007154), T (MESH:D001260), nontuberculous mycobacterial granulomas (MESH:D006099), skeletal defects (MESH:C567306), ATOs (MESH:D013953), SCID (MESH:D016511), radial ray defects (MESH:C564523), sepsis (MESH:D018805), BGS (MESH:C536788), ventriculomegaly (MESH:D006849), developmental delay (MESH:D002658) - **Chemicals:** fludarabine (MESH:C024352), cyclophosphamide (MESH:D003520), ATO (-) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606] - **Mutations:** c.2464-1G>C - **Cell lines:** MS5 — Mus musculus (Mouse), Stromal cell line (CVCL_2128) ## Figures 1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12965380/full.md --- Source: https://tomesphere.com/paper/PMC12965380