Late infantile neuronal ceroid lipofuscinosis is due to splicing mutations in the CLN2 gene

Mol Genet Metab. 1999 Jun;67(2):162-8. doi: 10.1006/mgme.1999.2853.

Abstract

Late infantile neuronal ceroid lipofuscinosis, LINCL, is one of the most common pediatric neurodegenerative disorders. It is caused by mutations in the CLN2 gene, which encodes a lysosomal pepstatin-insensitive peptidase (LPIP). We have identified a novel mutation, T523-1G --> A, by molecular analyses of three unrelated LINCL cases. The mutation was found to affect a 3' intronic splicing acceptor site, resulting in an aberrant mRNA with an insertion of 146 bp of intronic sequence. This causes a frame shift, produces a nonfunctional truncated protein, and results in LINCL.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine
  • Aminopeptidases
  • Child
  • Child, Preschool
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Endopeptidases
  • Female
  • Frameshift Mutation*
  • Gene Frequency
  • Guanine
  • Humans
  • Neuronal Ceroid-Lipofuscinoses / enzymology*
  • Neuronal Ceroid-Lipofuscinoses / genetics*
  • Neuronal Ceroid-Lipofuscinoses / pathology
  • Peptide Hydrolases / genetics*
  • RNA Splicing / genetics*
  • RNA, Messenger / genetics
  • Serine Proteases
  • Tripeptidyl-Peptidase 1

Substances

  • RNA, Messenger
  • Tripeptidyl-Peptidase 1
  • Guanine
  • Endopeptidases
  • Peptide Hydrolases
  • Serine Proteases
  • Aminopeptidases
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • TPP1 protein, human
  • Adenine