Novel de novo dominant <i>PSMB10</i> variants in three patients with immune deficiency and liver disease
Background and objective: Despite significant advances, the molecular basis and thus patient-tailored therapeutic options for inborn errors of immunity remain unknown in a significant number of patients. Methods: We investigated three patients from unrelated families with inborn errors of immunity and severe liver disease. Clinical, immunological, and histological (only in one patient for the latter) data were collected, and trio whole exome sequencing was performed. Results: Whole exome sequencing identified heterozygous de novo variants in PSMB10 (p.Asp205Ala and p.Ser208Phe), a gene encoding a specific subunit of the immuno- and thymoproteasome. Analysis showed poor integration into the proteasome complex of PSMB10 variants, thereby exerting a dominant-negative effect on the PSMB9 subunit. Conclusion: Dominant PSMB10 variants should be considered in genetic screening for SCID and CID, especially in patients with associated liver disease. Very severe endothelial-like disease before and after HSCT and very poor outcomes after HSCT should weigh up the indication of HSCT.
Authors
- Frédéric Ebstein (ORCID: https://orcid.org/0000-0002-3729-7878)
- Bénédicte Neven (ORCID: https://orcid.org/0000-0001-8941-0935)
- Paul Bastard (ORCID: https://orcid.org/0000-0002-5926-8437)
- Étienne Merlin (ORCID: https://orcid.org/0000-0001-6527-7893)
- Despina Moshous (ORCID: https://orcid.org/0000-0001-6719-3693)
- Sébastien Küry (ORCID: https://orcid.org/0000-0001-5497-0465)
- Hélène Deutsch (ORCID: https://orcid.org/0009-0005-3215-3452)
- Monique Fabrè (ORCID: https://orcid.org/0000-0002-3081-2478)
- Jérémie Rosain (ORCID: https://orcid.org/0000-0002-2822-161X)
- Vincent Abramowski (ORCID: https://orcid.org/0000-0002-4953-5124)
- Martin Castelle (ORCID: https://orcid.org/0000-0001-9087-4411)
- Capucine Pïcard (ORCID: https://orcid.org/0000-0001-8788-5056)
- Isabelle Callebaut (ORCID: https://orcid.org/0000-0003-3124-887X)
- Jean‐Pierre de Villartay
- Stéphane Bezieau (ORCID: https://orcid.org/0000-0003-0095-1319)
- Benjamin Fournier (ORCID: https://orcid.org/0000-0002-4189-996X)
- Léa Poirier (ORCID: https://orcid.org/0009-0003-7400-8363)
Institutions
- Délégation Paris 5 (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université Paris Cité (FR)
- Centre Hospitalier Universitaire de Nantes (FR)
- Sorbonne Université (FR)
- Centre de Référence Déficits Immunitaires Héréditaires (FR)
- Sorbonne Paris Cité (FR)
- Laboratoire de Minéralogie & Cosmochimie du Muséum (FR)
- La Ligue Contre le Cancer (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- University of Clermont Auvergne (FR)
- Délégation Centre-Est (FR)
- Centre Hospitalier Universitaire de Clermont-Ferrand (FR)
- Dynamique du noyau (FR)
- Clermont Université (FR)
- Institut du Thorax (FR)
- Institut de minéralogie, de physique des matériaux et de cosmochimie (FR)
- Génétique Médicale & Génomique Fonctionelle (FR)
- Human Genetic of Infectious Diseases (FR)
- Institut des Maladies Génétiques Imagine (FR)
- Rockefeller University (US)
- Nantes Université (FR)
Publication Details
- Journal
- Journal of Human Immunity
- Published
- 2025-09-24
- DOI
- https://doi.org/10.70962/jhi.20250096
- Citations
- 1
- Primary Topic
- Immunodeficiency and Autoimmune Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.80
Funders
- Institut des maladies génétiques Imagine
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale