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Clin Immunol. 2015 Dec;161(2):366-72. doi: 10.1016/j.clim.2015.10.002. Epub 2015 Oct 19.

Susceptibility to infections, without concomitant hyper-IgE, reported in 1976, is caused by hypomorphic mutation in the phosphoglucomutase 3 (PGM3) gene.

Author information

1
Clinical Research Center, Karolinska Institutet, Department of Laboratory Medicine, Karolinska University Hospital, S-141 86 Huddinge, Sweden. Electronic address: karin.lundin@ki.se.
2
Clinical Research Center, Karolinska Institutet, Department of Laboratory Medicine, Karolinska University Hospital, S-141 86 Huddinge, Sweden.
3
Department of Microbiology, Clinic for Diagnostics and Intervention, Oslo University Hospital, Rikshospitalet, Box 4950, Nydalen, N-0424 Oslo, Norway; Department of Medical Biochemistry, Institute for Clinical Medicine, University of Oslo, Box 4950, Nydalen, N-0424 Oslo, Norway.
4
Department of Immunology, Genetics and Pathology, Uppsala University, S-751 85 Uppsala, Sweden.
5
Department of Medical Biochemistry, Institute for Clinical Medicine, University of Oslo, Box 4950, Nydalen, N-0424 Oslo, Norway.
6
Department of Microbiology, Clinic for Diagnostics and Intervention, Oslo University Hospital, Rikshospitalet, Box 4950, Nydalen, N-0424 Oslo, Norway; Institute for Cancer Research and Molecular Medicine, NTNU, 8905, N-7491 Trondheim, Norway.
7
Immunodeficiency Unit, Section of Clinical Immunology, Karolinska University Hospital, S-14186, Stockholm, Sweden.
8
Immunodeficiency Unit, Section of Clinical Immunology, Karolinska University Hospital, S-14186, Stockholm, Sweden; Clinical Immunology and Transfusion Medicine, Karolinska University Laboratory, Karolinska University Hospital, S-14186, Stockholm, Sweden.
9
Department of Immunology, Genetics and Pathology, Uppsala University, S-751 85 Uppsala, Sweden; Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, S-171 21, Stockholm, Sweden.
10
Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, S-141 86, Stockholm, Sweden.
11
Department of Clinical Microbiology, Umeå University, Sweden.
12
Clinical Research Center, Karolinska Institutet, Department of Laboratory Medicine, Karolinska University Hospital, S-141 86 Huddinge, Sweden; Immunodeficiency Unit, Section of Clinical Immunology, Karolinska University Hospital, S-14186, Stockholm, Sweden. Electronic address: edvard.smith@ki.se.

Abstract

Phosphoglucomutase 3 (PGM3) is an enzyme converting N-acetyl-glucosamine-6-phosphate to N-acetyl-glucosamine-1-phosphate, a precursor important for glycosylation. Mutations in the PGM3 gene have recently been identified as the cause of novel primary immunodeficiency with a hyper-IgE like syndrome. Here we report the occurrence of a homozygous mutation in the PGM3 gene in a family with immunodeficient children, described already in 1976. DNA from two of the immunodeficient siblings was sequenced and shown to encode the same homozygous missense mutation, causing a destabilized protein with reduced enzymatic capacity. Affected individuals were highly prone to infections, but lack the developmental defects in the nervous and skeletal systems, reported in other families. Moreover, normal IgE levels were found. Thus, belonging to the expanding group of congenital glycosylation defects, PGM3 deficiency is characterized by immunodeficiency, with or without increased IgE levels, and with variable forms of developmental defects affecting other organ systems.

KEYWORDS:

CDG; Congenital defects of glycosylation; N-acetylglucosamine-phosphate mutase; Primary immunodeficiency; hyper-IgE syndrome

PMID:
26482871
PMCID:
PMC4695917
DOI:
10.1016/j.clim.2015.10.002
[Indexed for MEDLINE]
Free PMC Article

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