Variable Syndromic Immunodeficiency in Patients with Biallelic PRIM1 Mutations.
J Clin Immunol
; 44(6): 129, 2024 May 22.
Article
en En
| MEDLINE
| ID: mdl-38773012
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos B
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Alelos
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Mutación
Límite:
Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
J Clin Immunol
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J. clin. immunol
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Journal of clinical immunology
Año:
2024
Tipo del documento:
Article
País de afiliación:
Alemania