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57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

12. - 15.09.2012, Erlangen

57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

The morphotype, and the residual TPP-1 enzyme activity correlate with the underlying mutations in theTPP1/CLN2gene of Neuronal Ceroid Lipofuscinoses Late Infantile and variant Juvenile.

Meeting Abstract

  • presenting/speaker Ines Noher de Halac - Hospital de Niños/Universidad Nacional de Córdoaba, CEMECO, Córdoba, Argentina
  • Patricia Pons - Hospital de Niños/Universidad Nacional de Córdoaba, CEMECO, Córdoba, Argentina
  • Noelia Carabelos - Hospital de Niños/Universidad Nacional de Córdoaba, CEMECO, Córdoba, Argentina
  • Norberto Guelbert - Hospital de Niños/Universidad Nacional de Córdoaba, CEMECO, Córdoba, Argentina
  • Raquel Dodelson de Kremer - Hospital de Niños/Universidad Nacional de Córdoaba, CEMECO, Córdoba, Argentina
  • Ines Adriana Cismondi - Hospital de Niños/Universidad Nacional de Córdoaba, CEMECO, Córdoba, Argentina
  • Graciela Irene Alonso - Hospital de Niños/Universidad Nacional de Córdoaba, CEMECO, Córdoba, Argentina
  • Ana María Oller-Ramirez - Hospital de Niños/Universidad Nacional de Córdoaba, CEMECO, Córdoba, Argentina
  • Romina Kohan - Hospital de Niños/Universidad Nacional de Córdoaba, CEMECO, Córdoba, Argentina

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnPP4.6

DOI: 10.3205/12dgnn083, URN: urn:nbn:de:0183-12dgnn0836

Published: September 11, 2012

© 2012 Noher de Halac et al.
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Outline

Text

CLN2 (OMIM #204500) is a children's neurodegenerative disorder resulting from a deficiency of the lysosomal enzyme Tripeptidyl-Peptidase-1 (TPP1) encoded by the geneTPP1/CLN2. Inheritance is autosomal recessive. The aim was to investigate the possible correlations among the clinical phenotypes “classical late infantile” (LI) or “variant juvenile” (vJ), the morphological phenotypes, residual enzyme activity, and the genotypes. Twenty five patients with enzyme deficiencies 0–10% of control's activity in leukocytes were genotyped and a skin biopsy was studied with transmission electronic microscopy. The genotypes were profiled in the patients, and in 39 relatives. The classic LI phenotype was present in about 50% of patients with new and known mutations. The same and other new and known mutations were associated with the vJ phenotype in another 50% of patients. The “classical” LI phenotype correlated with a morphotype showing curvilinear profiles of ceroid lipofuscin-like material. The ”variant juvenile phenotype” showed morphotypes with curvilinear profiles in 10/13 patients, or mixed bodies with finger print profiles in 3/13 patients. Residual enzyme activities of around 10% in leukocytes were stated only in the vJ phenotype, as well as a prevalence in 8/13 patients of the intronic mutations c.887-10A>G (intron 7), and c.89+5G>C (intron 2) , combined with different missense/nonsense mutations. Interestingly in the vJ phenotype correlated with intronic mutations in non-conserved sites, there might be some alternative splicing and therefore some residual protein. The residual activity in vJ patients with heterozygous combinations of other kind of mutations is still waiting for an explanation.