PGM3 was first reported in relation to autosomal receive immunodeficiency 23 in 1987 (Bjorksten B & Lundmar KM et al., PMID: 1245758; summarized by Zhang et al., 2014, 24589341). Immunodeficiency 23 is a rare congenital disorder of glycosylation caused by mutations in the PGM3 gene and characterized by neonatal to childhood onset of recurrent bacterial and viral infections, inflammatory skin diseases, atopic dermatitis and atopic diatheses, and marked serum IgE elevation. Early neurologic impairment is evident including developmental delay, intellectual disability, ataxia, dysarthria, sensorineural hearing loss, myoclonus and seizures.
PGM3 encodes a member of the phosphohexose mutase family. The encoded protein mediates both glycogen formation and utilization by catalyzing the interconversion of glucose-1-phosphate and glucose-6-phosphate. (O'Leary NA et al., 2016, PMID: 26553804)
Twelve variants (9 missense, 1 in-frame deletion, 1 frame-shift and 1 duplication) that have been reported in approximately 8 probands in 4 publications (Zhang Y, et al., 2014, PMID: 24589341; Sassi A, et al., 2014, PMID: 24698316; Lundin KE, et al., 2015, PMID: 26482871; Stray-Pedersen A et al., 2014 PMID: 24931394;), are included in this curation. The mechanism of disease for Immunodeficiency 23 is gene mutations result in the production of an enzyme with reduced activity.
This gene-disease relationship is also supported by experimental evidence including expression of enzymatic activity in mouse models (Greig KT, et al., 2007, PMID: 17548465). In summary, there is strong evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Congenital Disorder of Glycosylation Expert Panel on the meeting date 9/20/2023 (SOP Version 9).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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