A mutation in the ovine cathepsin D gene causes a congenital lysosomal storage disease with profound neurodegeneration.

ABSTRACT: The neuronal ceroid lipofuscinoses (NCLs) constitute a group of neurodegenerative storage diseases characterized by progressive psychomotor retardation, blindness and premature death. Pathologically, there is accumulation of autofluorescent material in lysosome-derived organelles in a variety of cell types, but neurons in the central nervous system appear to be selectively affected and undergo progressive death. In this report we show that a novel form of NCL, congenital ovine NCL, is caused by a deficiency in the lysosomal aspartyl proteinase cathepsin D. A single nucleotide mutation in the cathepsin D gene results in conversion of an active site aspartate to asparagine, leading to production of an enzymatically inactive but stable protein. This results in severe cerebrocortical atrophy a

SUBMITTER: Tyynela J 

PROVIDER: S-EPMC203370 | biostudies-literature | 2000 Jun

REPOSITORIES: biostudies-literature