Two Novel Homozygous Mutations in Phosphoglucomutase 3 Leading to Severe Combined Immunodeficiency, Skeletal Dysplasia, and Malformations.
Abnormalities, Multiple
/ genetics
Bone Diseases, Developmental
/ genetics
Child, Preschool
Face
/ abnormalities
Female
Humans
Infant
Infant, Newborn
Limb Deformities, Congenital
/ genetics
Male
Nervous System Diseases
/ genetics
Phosphoglucomutase
/ genetics
Severe Combined Immunodeficiency
/ genetics
Congenital disorders of glycosylation
N-Acetylphosphoglucosamine
PGM3
Phosphoglucomutase 3
Primary immunodeficiency
Severe combined immunodeficiency
Skeletal dysplasia
Journal
Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
07
12
2020
accepted:
27
01
2021
pubmed:
4
2
2021
medline:
4
2
2022
entrez:
3
2
2021
Statut:
ppublish
Résumé
Phosphoglucomutase 3 (PGM3) deficiency is a rare congenital disorder of glycosylation. Most of patients with autosomal recessive hypomorphic mutations in PGM3 encoding for phosphoglucomutase 3 present with eczema, skin and lung infections, elevated serum IgE, as well as neurological and skeletal features. A few PGM3-deficient patients suffer from a more severe disease with nearly absent T cells and severe skeletal dysplasia. We performed targeted next-generation sequencing on two kindred to identify the underlying genetic etiology of a severe combined immunodeficiency with developmental defect. We report here two novel homozygous missense variants (p.Gly359Asp and p.Met423Thr) in PGM3 identified in three patients from two unrelated kindreds with severe combined immunodeficiency, neurological impairment, and skeletal dysplasia. Both variants segregated with the disease in the two families. They were predicted to be deleterious by in silico analysis. PGM3 enzymatic activity was found to be severely impaired in primary fibroblasts and Epstein-Barr virus immortalized B cells from the kindred carrying the p.Met423Thr variant. Our findings support the pathogenicity of these two novel variants in severe PGM3 deficiency.
Identifiants
pubmed: 33534079
doi: 10.1007/s10875-021-00985-w
pii: 10.1007/s10875-021-00985-w
doi:
Substances chimiques
PGM3 protein, human
EC 5.4.2.2
Phosphoglucomutase
EC 5.4.2.2
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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