부산대학교 도서관

Background: Phosphoglucomutase‐3 (PGM3) deficiency is a congenital disorder of glycosylation (CDG) with hyperimmunoglobulin IgE, atopy, and a variable immunological phenotype; most reported patients display dysmorphic features. The aim of the study was to characterize the genotype and phenotype of individuals with newly identified compound heterozygous variants in the phosphate‐binding domain of PGM3 in order to better understand phenotypic differences between these patients and published cases. Methods: We analyzed PGM3 protein expression, PGM3 enzymatic activity, the presence of other gene variants within the N‐glycosylation pathway, and the clinical and immunological manifestations of two affected siblings. Results: Patients belonged to a non‐consanguineous family, presenting with atopic dermatitis, elevated levels of IgE, and CD4+ lymphopenia (a more severe phenotype was observed in Patient 2), but lacked dysmorphic features or neurocognitive impairment. Compound heterozygous PGM3 variants were identified, located in the phosphate‐binding domain of the enzyme. PGM3 expression was comparable to healthy donors, but L‐PHA binding in naïve‐CD4+ cells was decreased. Examination of exome sequence identified the presence of one additional candidate variant of unknown significance (VUS) in the N‐glycosylation pathway in Patient 2: a variant predicted to have moderate‐to‐high impact in ALG12. Conclusions: Our analysis revealed that L‐PHA binding is reduced in naïve‐CD4+ cells, which is consistent with decreased residual PGM3 enzymatic activity. Other gene variants in the N‐glycosylation pathway may modify patient phenotypes in PGM3 deficiency. This study expands the clinical criteria for when PGM3 deficiency should be considered among individuals with hyper‐IgE. [ABSTRACT FROM AUTHOR]