The neuronal ceroid lipofuscinoses program: A translational research experience in Argentina

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1852

Review

Kohan, Romina^1,2  Pesaola, Favio^1,3  Guelbert, Norberto¹  Pons, Patricia⁴  Maria Oller-Ramirez, Ana¹  Rautenberg, Gisela¹  Becerra, Adriana¹  Sims, Katherine⁵  Xin, Winnie⁵  Adriana Cismondi, Ines^1,2  Noher de Halac, Ines^1,2,3 

[1] Univ Nacl Cordoba, Fac Ciencias Med, Ctr Estudio Metabolopatias Congenitas CEMECO, RA-5014 Cordoba, Argentina

[2] Univ Nacl Cordoba, Fac Odontol, RA-5000 Cordoba, Argentina

[3] Consejo Nacl Invest Cient & Tecn, RA-1033 Buenos Aires, DF, Argentina

[4] Univ Nacl Cordoba, Fac Ciencias Med, Ctr Microscopia Elect, RA-5000 Cordoba, Argentina

[5] Massachusetts Gen Hosp, Dept Neurol, Ctr Genet Res CHGR, Boston, MA 02114 USA

关键词: Neuronal ceroid lipofuscinoses;    Algorithm;    Morphology;    Enzymes;    DNA variants;   

DOI  :  10.1016/j.bbadis.2015.05.003

来源: Elsevier

【 摘 要 】

Background: The Argentinean program was initiated more than a decade ago as the first experience of systematic translational research focused on NCL in Latin America. The aim was to overcome misdiagnoses and underdiagnoses in the region. Subjects: 216 NCL suspected individuals from 8 different countries and their direct family members. Methods: Clinical assessment, enzyme testing, electron microscopy, and DNA screening. Results and discussion: 1) The study confirmed NCL disease in 122 subjects. Phenotypic studies comprised epileptic seizures and movement disorders, ophthalmology, neurophysiology, image analysis, rating scales, enzyme testing, and electron microscopy, carried out under a consensus algorithm; 2) DNA screening and validation of mutations in genes PPT1 (CLN1), TPP1 (CLN2), CLN3, CLN5, CLN6, MFSD8 (CLN7), and CLN8: characterization of variant types, novel/known mutations and polymorphisms; 3) Progress of the epidemiological picture in Latin America; and 4) NCL-like pathology studies in progress. The Translational Research Program was highly efficient in addressing the misdiagnosis/underdiagnosis in the NCL disorders. The study of orphan diseases in a public administrated hospital should be adopted by the health systems, as it positively impacts upon the family's quality of life, the collection of epidemiological data, and triggers research advances. This article is part of a Special Issue entitled: Current Research on the Neuronal Ceroid Lipofuscinoses (Batten Disease). (C) 2015 Elsevier B.V. All rights reserved.

【 授权许可】

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