Genotype-phenotype correlations in neuronal ceroid lipofuscinosis due to palmitoyl-protein thioesterase deficiency

Mol Genet Metab. 1999 Apr;66(4):234-9. doi: 10.1006/mgme.1999.2803.


The infantile form of neuronal ceroid lipofuscinosis (NCL) has been well studied in Finland, where there is a high carrier frequency (1:70) for a single mutation in the causative gene, CLN1, or PPT. We have recently studied a group of 29 NCL subjects in the United States with palmitoyl-protein thioesterase (PPT) deficiency and described 19 different CLN1/PPT mutations in our population. In this report, we present a review of our previous findings, including a more detailed analysis of phenotype-genotype correlations, and present previously unpublished data concerning the clinical manifestations of the disorder in children of families with multiple affected members. Our studies indicate that about half of PPT-deficient patients in the United States are very similar to Finnish infants with INCL, but that a different mutation (R151X) accounts for 40% of U.S. alleles. The Finnish mutation (R122W) is rare in the United States. The other half of U.S. PPT-deficient patients develop symptoms after the age of 2 years, much later than Finnish patients. One common mutation (the "Scottish" allele, T75P) accounts for 13% of alleles and results in a juvenile-onset phenotype that is clinically indistinguishable from JNCL with CLN3 mutations. Other rare mutations were also associated with JNCL phenotypes, such as D79G and G250V. A preliminary expression study of two of these mutant enzymes supports the conclusion that juvenile-onset NCL (JNCL with GROD) is caused by missense mutations in the PPT gene that result in mutated enzymes with residual PPT enzyme activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age of Onset
  • Animals
  • COS Cells
  • Child
  • Child, Preschool
  • Genotype
  • Humans
  • Immunoblotting
  • Infant
  • Microscopy, Electron
  • Mutagenesis, Site-Directed
  • Neuronal Ceroid-Lipofuscinoses / genetics*
  • Phenotype
  • Point Mutation
  • Thiolester Hydrolases / deficiency*
  • Thiolester Hydrolases / metabolism
  • Transfection


  • Thiolester Hydrolases
  • palmitoyl-protein thioesterase