De novo loss-of-function variant in PTDSS1 is associated with developmental delay.

ABSTRACT: Heterozygous de novo missense pathogenic variants in PTDSS1 that result in gain-of-function of phosphatidylserine synthase 1 are associated with Lenz-Majewski hyperostotic dwarfism (LMHD). We identified the novel heterozygous de novo variant p.(Leu137Phe) in PTDSS1 in a child with mild-to-moderate developmental delay. Skeletal survey revealed no evidence of LMHD in this patient. Functional assessment of the p.Leu137Phe variant was performed by overexpressing the mutant protein into HEK293 cells. Following C¹⁴ -serine labeling and TLC analysis of lipids, we observed that the p.(Leu137Phe) variant displayed no catalytic activity compared to the wild-type enzyme. We conclude that p.(Leu137Phe) variant has decreased enzymatic activity and that is likely to be the etiology of the pat

SUBMITTER: Gracie S 

PROVIDER: S-EPMC9179020 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature