GFPT1 was first reported in relation to autosomal recessive congenital myasthenic syndrome 12 in 2011 (Senderek et al., PMID: 21310273). Twelve variants (missense, nonsense, frameshift, splicing) that have been reported in 8 probands in 2 publications (PMIDs: 21310273, 23794683) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts) has been reached. Congenital myasthenic syndrome 12 is characterized by limb-girdle muscle weakness and tubular aggregates on muscle biopsies. The disease mechanism appears to be biallelic loss of function. Heterozygous carriers are reportedly unaffected. This gene-disease relationship is also supported by the biochemical function of GFPT1, which is involved in the hexosamine biosynthesis pathway that serves as a source of essential amino sugars for the synthesis of glycoproteins, glycolipids, and proteoglycans, animal models that recapitulate disease, and expression in skeletal muscle (PMIDs: 21310273, 29905857, 11679416). In summary, there is definitive evidence supporting the relationship between GFPT1 and to autosomal recessive congenital myasthenic syndrome 12.This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on the meeting date July 3, 2024 (SOP Version 10).
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).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.