Susceptibility to infections, without concomitant hyper-IgE, reported in 1976, is caused by hypomorphic mutation in the phosphoglucomutase 3 (PGM3) gene.
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.
Clinical Research Center, Karolinska Institutet, Department of Laboratory Medicine, Karolinska University Hospital, S-141 86 Huddinge, Sweden. Electronic address: karin.lundin@ki.se.
Karin E
KE
Lundin
Clinical Research Center, Karolinska Institutet, Department of Laboratory Medicine, Karolinska University Hospital, S-141 86 Huddinge, Sweden.
Abdulrahman
A
Hamasy
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.
Paul Hoff
PH
Backe
Department of Immunology, Genetics and Pathology, Uppsala University, S-751 85 Uppsala, Sweden.
Lotte N
LN
Moens
Department of Immunology, Genetics and Pathology, Uppsala University, S-751 85 Uppsala, Sweden.
Elin
E
Falk-Sörqvist
Department of Medical Biochemistry, Institute for Clinical Medicine, University of Oslo, Box 4950, Nydalen, N-0424 Oslo, Norway.
Katja B
KB
Elgstøen
Department of Medical Biochemistry, Institute for Clinical Medicine, University of Oslo, Box 4950, Nydalen, N-0424 Oslo, Norway.
Lars
L
Mørkrid
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.
Magnar
M
Bjørås
Immunodeficiency Unit, Section of Clinical Immunology, Karolinska University Hospital, S-14186, Stockholm, Sweden.
Carl
C
Granert
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.
Anna-Carin
AC
Norlin
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.
Mats
M
Nilsson
Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, S-141 86, Stockholm, Sweden.
Birger
B
Christensson
Department of Clinical Microbiology, Umeå University, Sweden.
Stephan
S
Stenmark
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.
C I Edvard
CI
Smith
D000328:Adult; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D005192:Family Health; D017809:Fatal Outcome; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000378:metabolism; D007239:Infections / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010733:Phosphoglucomutase / Q000235:genetics* / Q000378:metabolism; D035781:Siblings
C549916:PGM3 protein, human; D010733:Phosphoglucomutase
CDG; Congenital defects of glycosylation; N-acetylglucosamine-phosphate mutase; Primary immunodeficiency; hyper-IgE syndrome