Large-scale functional LIPA variant characterization to improve birth prevalence estimates of lysosomal acid lipase deficiency.

ABSTRACT: Lysosomal acid lipase (LAL) deficiency is an autosomal recessive disorder caused by LIPA gene mutations that disrupt LAL activity. We performed in vitro functional testing of 149 LIPA variants to increase the understanding of the variant effects on LAL deficiency and to improve disease prevalence estimates. Chosen variants had been reported in literature or population databases. Functional testing was done by plasmid transient transfection and LAL activity assessment. We assembled a set of 165 published LAL deficient patient genotypes to evaluate this assay's effectiveness to recapitulate genotype/phenotype relationships. Rapidly progressive LAL deficient patients showed negligible enzymatic activity (<1%), whereas patients with childhood/adult LAL deficiency typically have 1-7% average ac

SUBMITTER: Del Angel G 

PROVIDER: S-EPMC6852163 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature