Large scale analyses of genotype-phenotype relationships of glycine decarboxylase mutations and neurological disease severity.

ABSTRACT: Monogenetic diseases provide unique opportunity for studying complex, clinical states that underlie neurological severity. Loss of glycine decarboxylase (GLDC) can severely impact neurological development as seen in non-ketotic hyperglycinemia (NKH). NKH is a neuro-metabolic disorder lacking quantitative predictors of disease states. It is characterized by elevation of glycine, seizures and failure to thrive, but glycine reduction often fails to confer neurological benefit, suggesting need for alternate tools to distinguish severe from attenuated disease. A major challenge has been that there are 255 unique disease-causing missense mutations in GLDC, of which 206 remain entirely uncharacterized. Here we report a Multiparametric Mutation Score (MMS) developed by combining in silico predicti

SUBMITTER: Farris J 

PROVIDER: S-EPMC7259800 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature