Congenital Disorders of Glycosylation

Gene: GFPT1

Green List (high evidence)

15 unrelated families reported with bi-allelic variants and a congenital myasthenic syndrome. Two families with leukoencephalopathy as well as CMS.

The GFPT1 gene encodes an isoform of glutamine:fructose-6-phosphate amidotransferase (GFAT), which catalyzes the transfer of an amino group from glutamine onto fructose-6-phosphate, yielding glucosamine 6-phosphate and glutamate. It is the first and rate-limiting enzyme of the hexosamine biosynthetic pathway. Hexosamine is the obligatory source of essential amino sugars for the synthesis of glycoproteins, glycolipids, and proteoglycans. Muscle samples from several patients showed decreased protein glycosylation, suggesting this is a disorder of glycosylation. However, there is also some data put forward in PMID 30635494 that this may be a mitochondrial condition.

Created: 24 Oct 2020, 8:49 a.m. | Last Modified: 24 Oct 2020, 8:51 a.m.

Panel Version: 0.173

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myasthenia, congenital, 12, with tubular aggregates, 610542; Limb-girdle congenital myasthenic syndrome; Leukoencephalopathy

Publications

• 21310273
• 30635494