Heterogeneity of late-infantile neuronal ceroid lipofuscinosis

Genet Med. Nov-Dec 2000;2(6):312-8. doi: 10.1097/00125817-200011000-00002.


Purpose: Late-infantile neuronal ceroid lipofuscinosis (LINCL), an autosomal recessively inherited lysosomal storage disorder characterized by autofluorescent inclusions and rapid progression of neurodegeneration, is due to CLN2 gene mutations. However, CLN2 mutation analysis has failed to identify some clinically diagnosed "late-infantile" NCL cases. This study was conducted to further characterize genetic heterogeneity in families affected by LINCL.

Methods: DNA mutations in the CLN1, CLN2, and CLN3 genes that underlie INCL (infantile NCL), LINCL, and JNCL (juvenile NCL), respectively, were studied with molecular analyses.

Results: A total of 252 families affected by childhood NCL were studied. Of 109 families clinically diagnosed as having LINCL, 3 were determined to have either INCL or JNCL by identification of mutation(s) in CLN1 or CLN3. Six families diagnosed initially as having JNCL were found to have LINCL based on the finding of mutations in the CLN2 gene. In addition, several novel mutations were identified.

Conclusions: Clinical and genetic heterogeneity of LINCL was demonstrated in nine LINCL families studied.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopeptidases
  • Child
  • Child, Preschool
  • DNA Mutational Analysis / methods
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Endopeptidases
  • Genetic Heterogeneity*
  • Genetic Markers
  • Genetic Testing
  • Humans
  • Infant
  • Membrane Glycoproteins*
  • Membrane Proteins / genetics*
  • Molecular Chaperones*
  • Mutation / genetics
  • Neuronal Ceroid-Lipofuscinoses / diagnosis
  • Neuronal Ceroid-Lipofuscinoses / genetics*
  • Peptide Hydrolases / classification
  • Peptide Hydrolases / genetics*
  • Polymerase Chain Reaction
  • Proteins / genetics
  • Serine Proteases
  • Thiolester Hydrolases


  • CLN3 protein, human
  • Genetic Markers
  • Membrane Glycoproteins
  • Membrane Proteins
  • Molecular Chaperones
  • Proteins
  • Thiolester Hydrolases
  • PPT1 protein, human
  • Endopeptidases
  • Peptide Hydrolases
  • Serine Proteases
  • Aminopeptidases
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • tripeptidyl-peptidase 1