Abstract |
Tripeptidyl-peptidase 1 (TPP1) null or residual activity occurs in neuronal ceroid lipofuscinosis (NCL) with underlying TPP1/CLN2 mutations. A survey of 25 South American CLN2 affected individuals enabled the differentiation of two phenotypes: classical late-infantile and variant juvenile, each in approximately 50% of patients, with residual TPP1 activity occurring in approximately 32%. Each individual was assigned to one of three subgroups: (I) n=11, null TPP1 activity in leukocytes; (II) n=8, residual TPP1 activity of 0.60-15.85 nmol/h/mg (nr 110-476); (III) n=6, activity not measured in leukocytes. Curvilinear bodies (CB) appeared in almost all studied CLN2 subjects; the only exceptions occurred in cases of subgroup II: two individuals had combined CBs/fingerprints (FPs), and one case had pure FPs. There were 15 mutations (4 first published in this paper, 3 previously observed in South America by our group, and 8 previously observed by others). In subgroup I, mutations were either missense or nonsense; in subgroups II and III, mutations prevailed at the non-conserved intronic site, c.887-10A>G (intron 7), and to a lesser extent at c.89+5G>C (intron 2), in heterozygous combinations. Grouping phenotypically and genetically known individuals on the basis of TPP1 activity supported the concept that residual enzyme activity underlies a protracted disease course. The prevalence of intronic mutations at non-conserved sites in subgroup II individuals indicates that some alternative splicing might allow some residual TPP1 activity.
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Authors | Romina Kohan, María Noelia Carabelos, Winnie Xin, Katherine Sims, Norberto Guelbert, Inés Adriana Cismondi, Patricia Pons, Graciela Irene Alonso, Mónica Troncoso, Scarlet Witting, David A Pearce, Raquel Dodelson de Kremer, Ana María Oller-Ramírez, Inés Noher de Halac |
Journal | Gene
(Gene)
Vol. 516
Issue 1
Pg. 114-21
(Mar 01 2013)
ISSN: 1879-0038 [Electronic] Netherlands |
PMID | 23266810
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Elsevier B.V. All rights reserved. |
Chemical References |
- Tripeptidyl-Peptidase 1
- Serine Proteases
- Aminopeptidases
- Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
- TPP1 protein, human
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Topics |
- Adolescent
- Adult
- Alleles
- Alternative Splicing
- Aminopeptidases
(genetics, metabolism)
- Argentina
- Child
- Child, Preschool
- Computational Biology
- Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
(genetics, metabolism)
- Female
- Humans
- Introns
- Male
- Microscopy, Electron, Transmission
- Mutation
- Neuronal Ceroid-Lipofuscinoses
(enzymology, genetics, pathology)
- Pedigree
- Phenotype
- Prospective Studies
- Reproducibility of Results
- Retrospective Studies
- Serine Proteases
(genetics, metabolism)
- South America
- Tripeptidyl-Peptidase 1
- Young Adult
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