gms | German Medical Science

57. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie (DGNN)

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie

12. - 15.09.2012, Erlangen

Banner: 57. Jahrestagung der Deutschen Gesellschaft fŘr Neuropathologie und Neuroanatomie

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 Ni˝os/Universidad Nacional de Cˇrdoaba, CEMECO, Cˇrdoba, Argentina
  • Patricia Pons - Hospital de Ni˝os/Universidad Nacional de Cˇrdoaba, CEMECO, Cˇrdoba, Argentina
  • Noelia Carabelos - Hospital de Ni˝os/Universidad Nacional de Cˇrdoaba, CEMECO, Cˇrdoba, Argentina
  • Norberto Guelbert - Hospital de Ni˝os/Universidad Nacional de Cˇrdoaba, CEMECO, Cˇrdoba, Argentina
  • Raquel Dodelson de Kremer - Hospital de Ni˝os/Universidad Nacional de Cˇrdoaba, CEMECO, Cˇrdoba, Argentina
  • Ines Adriana Cismondi - Hospital de Ni˝os/Universidad Nacional de Cˇrdoaba, CEMECO, Cˇrdoba, Argentina
  • Graciela Irene Alonso - Hospital de Ni˝os/Universidad Nacional de Cˇrdoaba, CEMECO, Cˇrdoba, Argentina
  • Ana MarÝa Oller-Ramirez - Hospital de Ni˝os/Universidad Nacional de Cˇrdoaba, CEMECO, Cˇrdoba, Argentina
  • Romina Kohan - Hospital de Ni˝os/Universidad Nacional de Cˇrdoaba, CEMECO, Cˇrdoba, Argentina

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

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

Veröffentlicht: 11. September 2012

© 2012 Noher de Halac et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfńltigt, verbreitet und ÷ffentlich zugńnglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

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.