Neuronal ceroid lipofuscinosis type CLN2: a new rationale for the construction of phenotypic subgroups based on a survey of 25 cases in South America.

Autor: Kohan R; Centro de Estudio de las Metabolopatías Congénitas (CEMECO), Cátedra de Clínica Pediátrica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Ferroviarios 1250, (5014) Córdoba, Argentina., Carabelos MN, Xin W, Sims K, Guelbert N, Cismondi IA, Pons P, Alonso GI, Troncoso M, Witting S, Pearce DA, Dodelson de Kremer R, Oller-Ramírez AM, Noher de Halac I
Jazyk: angličtina
Zdroj: Gene [Gene] 2013 Mar 01; Vol. 516 (1), pp. 114-21. Date of Electronic Publication: 2012 Dec 22.
DOI: 10.1016/j.gene.2012.12.058
Abstrakt: 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.
(Copyright © 2013 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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