"Niemann-Pick disease type C1 (NPC1) is a severe neurovisceral lysosomal storage disorder with significant psychosocial impacts for affected families and, due to financial costs, also for the healthcare systems. Accurate NPC1 diagnostics are fundamental prerequisites for any therapy. Moreover, drugs currently used for clinical treatment of NPC, even though not targeting the primary cause, are expensive and their application must be rationalized. The aim of the project is to characterize molecular consequences of NPC1 mutations on mRNA and protein levels and to test selected mutants for their responsiveness to chaperone treatment. NPC1 promoter will be studied to show if its polymorphisms or other sequence variants influence transcription levels and thus contribute to NPC1 pathogenesis. The results of the laboratory analyses correlated to clinical severity and quality-of-life data will enable a critical selection of standards to be embedded into newly introduced diagnostic algorithm of NPC1 disease."@en . "Niemann-Pick disease type C1; clinical study; molecular genetic analysis; immunocytochemistry; diagnostic standards; chaperone treatment"@en . . . "Niemann-Pickova choroba typ C1 (NPC1) je z\u00E1va\u017En\u00E9 neuroviscer\u00E1ln\u00ED lysosom\u00E1ln\u00ED st\u0159\u00E1dac\u00ED onemocn\u011Bn\u00ED s v\u00FDznamn\u00FDmi psychosoci\u00E1ln\u00EDmi dopady pro posti\u017Een\u00E9 rodiny a z hlediska finan\u010Dn\u00EDho i pro zdravotn\u00ED syst\u00E9m jako celek. Kauz\u00E1ln\u00ED terapie NPC1 nen\u00ED v tuto chv\u00EDli dostupn\u00E1. Aplikace p\u0159\u00EDpravk\u016F zav\u00E1d\u011Bn\u00FDch do klinick\u00E9 praxe je n\u00E1kladn\u00E1 a proto je rychl\u00E1 a efektivn\u00ED diagnostika NPC1 nutn\u00FDm p\u0159edpokladem \u00FAsp\u011Bchu terapeutick\u00E9ho z\u00E1sahu, stejn\u011B jako racionalizace jejich pod\u00E1n\u00ED. V projektu navrhovan\u00E1 specifikace molekul\u00E1rn\u011B patofysiologick\u00FDch d\u016Fsledk\u016F mutac\u00ED genu NPC1 na \u00FArovni mRNA a proteinu pom\u016F\u017Ee ur\u010Dit efekt nov\u00FDch zp\u016Fsob\u016F l\u00E9\u010Dby. Funk\u010Dn\u00ED studie promotorov\u00E9 oblasti genu NPC1 uk\u00E1\u017Ee, zda polymorfismy nebo dal\u0161\u00ED nalezen\u00E9 genetick\u00E9 zm\u011Bny ovliv\u0148uj\u00ED \u00FArove\u0148 transkripce a t\u00EDm se pod\u00EDlej\u00ED na molekul\u00E1rn\u00ED patogenezi NPC1. Navrhovan\u00E1 laboratorn\u00ED vy\u0161et\u0159en\u00ED v korelaci s klinick\u00FDmi \u00FAdaji umo\u017En\u00ED ur\u010Dit nejen postupy vhodn\u00E9 k za\u0159azen\u00ED mezi diagnostick\u00E9 standardy ale i jejich vyu\u017Eitelnost v nov\u011B vytv\u00E1\u0159en\u00E9m diagnostick\u00E9m algoritmu NPC1." . . "Niemann-Pickova choroba typu C: klinick\u00E1, molekul\u00E1rn\u011B genetick\u00E1, biochemick\u00E1 a morfologick\u00E1 studie. N\u00E1vrh nov\u00FDch diagnostick\u00FDch a prediktivn\u00EDch algoritm\u016F" . "2015-01-22+01:00"^^ . "1"^^ . . " immunocytochemistry" . "1"^^ . " molecular genetic analysis" . . . "1"^^ . . . "2014-03-21+01:00"^^ . "2"^^ . . "2011-06-01+02:00"^^ . "2015-12-31+01:00"^^ . . "http://www.isvav.cz/projectDetail.do?rowId=NT12239"^^ . . . "NT12239" . . . "0"^^ . "Niemann-Pick disease type C : clinical, molecular genetic, biochemical and morphological study. Development of new diagnostic and predictive algorithms"@en . " clinical study" . . "Niemann-Pick disease type C1" . . . " diagnostic standards" .