Susceptibility to infections, without concomitant hyper-IgE, reported in 1976, is caused by hypomorphic mutation in the phosphoglucomutase 3 (PGM3) gene
| Autor: | Abdulrahman Hamasy, C. I. Edvard Smith, Katja Benedikte Prestø Elgstøen, Mats Nilsson, Carl Granert, Lars Mørkrid, Elin Falk-Sörqvist, Paul Hoff Backe, Stephan Stenmark, Karin E. Lundin, Birger Christensson, Lotte Moens, Anna-Carin Norlin, Magnar Bjørås |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
UDP-GalNac uridine diphosphate N-acetylglucosamine DNA Mutational Analysis medicine.disease_cause chemistry.chemical_compound Fatal Outcome 0302 clinical medicine Immunology and Allergy Missense mutation Cells Cultured Immunodeficiency Genetics 0303 health sciences Mutation Primary immunodeficiency Middle Aged Increased IgE level Pedigree 3. Good health Congenital fects of glycosylation Female Phosphoglucomutase Adult Glycosylation EBV Epstein Barr Virus Blotting Western Immunology Congenital defects of glycosylation GlcNAc-1-P N-acetyl-glucosamine-1-phosphate Biology Infections Article 03 medical and health sciences hyper-IgE syndrome medicine CDG Congenital defects in glycosylation Humans Genetic Predisposition to Disease Gene N-acetylglucosamine-phosphate mutase 030304 developmental biology Family Health Base Sequence GlcNAc-6-P N-acetyl-glucosamine-6-phosphate Siblings Immunologic Deficiency Syndromes HIES hyper-IgE syndrome Immunology in the medical area PGM3 Phosphoglucomutase 3 medicine.disease N-acetylglucosamine-phosphate mutase hyper-IgE syndrome chemistry Immunologi inom det medicinska området CDG 030217 neurology & neurosurgery |
| Zdroj: | Clinical Immunology (Orlando, Fla.) |
| Popis: | 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. Highlights • Immunodeficiency reported in 1976, is now identified as caused by a mutation in PGM3. • Replacing Ile322 with Thr reduces protein stability and enzyme activity in PGM3. • Identified mutation in PGM3 induces primary immunodeficiency without hyper-IgE. • A PGM3-PID with increased eosinophils but without skeletal or neurological changes |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|