Variable syndromic immunodeficiency in patients with Biallelic PRIM1 mutations

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Abstract: Mutations in genes of the DNA polymerase complex have been linked to impaired immunological function next to distinct syndromic features. Biallelic mutations in PRIM1 are associated with a primordial dwarfism syndrome with variable hypogammaglobulinemia. The disease is mostly lethal in infancy due to pulmonary infections as well as hepatic cirrhosis. We studied 3 novel patients with PRIM1-deficiency with a focus on immunological consequences. All three shared dysmorphic features including a prominent forehead, triangular face and bilateral cryptorchidism. P1 carried the novel homozygous PRIM1 splice variant c.103+2T>G, allowing residual protein expression and associated with a mild clinical phenotype. P2 and P3 carried the known homozygous variant c.638+36C>G and died in infancy. Paradoxically, B cell lymphopenia was most pronounced in P1. No other significant lymphocyte abnormalities were detected. Interestingly, all 3 patients showed variable, but intermittently excessive Type I interferon signatures. In summary, the B-cell deficiency in PRIM1-deficiency is markedly variable and the severity of syndromic manifestations is not predictive of the immunological phenotype. We highlight a potential contribution of pathological type I interferon activation to disease pathogenesis which warrants further investigations

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Notes: Journal of clinical immunology. - 44, 6 (2024) , 129, ISSN: 1573-2592

Event: Veröffentlichung

(where): Freiburg

(who): Universität

(when): 2024

Creator: Toskov, Vasil
Kaiser-Labusch, Petra
Lee-Kirsch, Min Ae
Ehl, Stephan
Wegehaupt, Oliver Philipp
Speckmann, Carsten

DOI: 10.1007/s10875-024-01733-6

URN: urn:nbn:de:bsz:25-freidok-2491198

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 14.08.2025, 10:52 AM CEST

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Associated

Toskov, Vasil
Kaiser-Labusch, Petra
Lee-Kirsch, Min Ae
Ehl, Stephan
Wegehaupt, Oliver Philipp
Speckmann, Carsten
Universität

Time of origin

2024

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