Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Mar 1;516(1):114-21.
doi: 10.1016/j.gene.2012.12.058. Epub 2012 Dec 22.

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

Romina Kohan  1 , 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
Affiliations

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

Romina Kohan et al. Gene. .

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.

PubMed Disclaimer

Conflict of interest statement

We declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Genealogies. (A) 82-2219 (III-2) and 82-1806 (II-7); (B) 173-1307 (II-3) and 173-1308 (II-2); C) 117-1312 (IV-3); and (D) 147-1805 (II-4) and 147-1807 (II-5). Although II-7 and II-2 were not screened, their genotypes were deduced from those of their relatives.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR. A method and server for predicting damaging missense mutations. Nat. Methods. 2010;7:248–249. [PubMed: 20354512] - PMC - PubMed
    1. Arsov T, Smith KR, Damiano J, Franceschetti S, Canafoglia L, Bromhead CJ, Andermann E, Vears DF, Cossette P, Rajagopalan S, McDougall A, Sofia V, Farrell M, Aguglia U, Zini A, Meletti S, Morbin M, Mullen S, Andermann F, Mole SE, Bahlo M, Berkovic SF. Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6. Am. J Hum. Genet. 2011;88:566–573. [PubMed: 21549341] - PMC - PubMed
    1. Bessa C, Teixeira CA, Dias A, Alves M, Rocha S, Lacerda L, Loureiro L, Guimaraes A, Ribeiro MG. CLN2/TPP1 deficiency: the novel mutation IVS7-10A>G causes intron retention and is associated with a mild disease phenotype. Mol. Genet. Metab. 2008;93:66–73. [PubMed: 17959406] - PubMed
    1. Bras J, Verloes A, Schneider SA, Mole SE, Guerreiro RJ. Mutation of the parkinsonism gene ATP13A2 causes neuronal ceroid-lipofuscinosis. Hum. Mol. Genet. 2012;21:2646–2650. [PubMed: 22388936] - PMC - PubMed
    1. Cox TM, Cachon-Gonzalez MB. The cellular pathology of lysosomal diseases. J Pathol. 2012;226:241–254. [PubMed: 21990005] - PubMed

Publication types

MeSH terms