Severe early-onset obesityGene: PGM2L1
Comment on list classification: New gene added by Zornitza Stark. There is sufficient evidence to promote this gene to Green at the next GMS panel update (tagged).
Morava et al. 2021 (PMID: 33979636) identified 4 unrelated individuals with different biallelic protein-truncating variants in the PGM2L1 gene. All had severe GDD/ID. Other features that reach the threshold for inclusion on the relevant panels (observed in at least 3 cases) are epilepsy and early obesity (99th centile at ages 2 to 3). Some functional data included.
Created: 12 Aug 2021, 3:42 p.m. | Last Modified: 12 Aug 2021, 3:42 p.m.
Panel Version: 3.1218
- Bi-allelic PTVs in 4 unrelated individuals. All four affected individuals had severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris. Early obesity and seizures were present in three individuals.
- Studies on patient fibroblasts and cell lines indicated that PGM2L1 deficiency causes a decrease, but not a disappearance, of the sugar bisphosphates needed for the formation of NDP-sugars and that there is no evidence that this leads to a glycosylation defect.
Created: 12 Jun 2021, 3:14 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Tag gene-checked tag was added to gene: PGM2L1.
gene: PGM2L1 was added gene: PGM2L1 was added to Severe early-onset obesity. Sources: Expert Review Amber,Literature Q3_21_rating tags were added to gene: PGM2L1. Mode of inheritance for gene: PGM2L1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PGM2L1 were set to 33979636 Phenotypes for gene: PGM2L1 were set to Neurodevelopmental disorder