[Tripeptidyl peptidase 1 deficiency in neuronal ceroid lipofuscinosis. A novel mutation]

Vopr Med Khim. 2002 Nov-Dec;48(6):594-8.
[Article in Russian]

Abstract

The data on biochemical and molecular-genetic diagnostics of a hereditary lisosomal storage disease, late infantile neuronal ceroid lipofuscinosis (CLN2) are presented. The disease is associated with a hereditary deficiency of pepstatin-unsensitive peptidase--tripeptidylpeptidase 1 (TPP1)--caused by mutations in the TPP1-coding gene CLN2. Among the 30 patients with clinical manifestations of CLN, six patients with a pronounced decrease in TPP1 activity were revealed; these data were interpreted as indicating the presence of CLN2 in these patients. The analysis of the isolated DNA indicated the availability of the most widespread mutation g3670 C > T(R208X) leading to the untimely termination of TPP1 synthesis. It was shown that in 5 patients this mutation is present in homozygous state and in one patient, in the heterozygous state. In this patient a hitherto unknown mutation, g3665G > A (R206H), was revealed. The pathogenetic significance of this mutation and the importance of molecular-genetic diagnosis of CLN are discussed with regard to medico-genetic consulting and prenatal diagnosis of this disease.

MeSH terms

  • Amino Acid Sequence
  • Aminopeptidases
  • Child
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Endopeptidases / deficiency
  • Endopeptidases / genetics*
  • Humans
  • Mutation
  • Neuronal Ceroid-Lipofuscinoses / diagnosis
  • Neuronal Ceroid-Lipofuscinoses / genetics*
  • Serine Proteases
  • Tripeptidyl-Peptidase 1

Substances

  • Tripeptidyl-Peptidase 1
  • Endopeptidases
  • Serine Proteases
  • Aminopeptidases
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • TPP1 protein, human