The Large Phenotypic Spectrum of Fabry Disease Requires Graduated Diagnosis and Personalized Therapy: A Meta-Analysis Can Help to Differentiate Missense Mutations
| Autor: | Valentina Citro 1, Marco Cammisa 2, Ludovica Liguori 3, Chiara Cimmaruta 1, 3, Jan Lukas 4, Maria Vittoria Cubellis 1, Giuseppina Andreotti 3 |
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| Přispěvatelé: | Citro, Valentina, Cammisa, Marco, Liguori, Ludovica, Cimmaruta, Chiara, Lukas, Jan, Cubellis, MARIA VITTORIA, Andreotti, Giuseppina |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Fabry disease/drug therapy Mutant Mutation Missense Bioinformatics Catalysis Article α-galactosidase pharmacological chaperones 1-deoxynojirimycin Inorganic Chemistry Small Molecule Libraries lcsh:Chemistry 03 medical and health sciences ?-galactosidase Genotype medicine Missense mutation Humans Physical and Theoretical Chemistry Precision Medicine Molecular Biology lcsh:QH301-705.5 Spectroscopy Genetics biology business.industry Organic Chemistry General Medicine Transfection medicine.disease Phenotype Fabry disease In vitro Computer Science Applications pharmacological chaperone 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 Chaperone (protein) alpha-Galactosidase biology.protein Fabry Disease business Molecular Chaperones |
| Zdroj: | International journal of molecular sciences (Online) (2016). doi:10.3390/ijms17122010 info:cnr-pdr/source/autori:Valentina Citro 1, Marco Cammisa 2, Ludovica Liguori 3, Chiara Cimmaruta 1,3, Jan Lukas 4,*, Maria Vittoria Cubellis 1,* and Giuseppina Andreotti 3/titolo:The Large Phenotypic Spectrum of Fabry Disease Requires Graduated Diagnosis and Personalized Therapy: A Meta-Analysis Can Help to Differentiate Missense Mutations/doi:10.3390%2Fijms17122010/rivista:International journal of molecular sciences (Online)/anno:2016/pagina_da:/pagina_a:/intervallo_pagine:/volume International Journal of Molecular Sciences, Vol 17, Iss 12, p 2010 (2016) International Journal of Molecular Sciences International Journal of Molecular Sciences; Volume 17; Issue 12; Pages: 2010 |
| DOI: | 10.3390/ijms17122010 |
| Popis: | Fabry disease is caused by mutations in the GLA gene and is characterized by a large genotypic and phenotypic spectrum. Missense mutations pose a special problem for graduating diagnosis and choosing a cost-effective therapy. Some mutants retain enzymatic activity, but are less stable than the wild type protein. These mutants can be stabilized by small molecules which are defined as pharmacological chaperones. The first chaperone to reach clinical trial is 1-deoxygalactonojirimycin, but others have been tested in vitro. Residual activity of GLA mutants has been measured in the presence or absence of pharmacological chaperones by several authors. Data obtained from transfected cells correlate with those obtained in cells derived from patients, regardless of whether 1-deoxygalactonojirimycin was present or not. The extent to which missense mutations respond to 1-deoxygalactonojirimycin is variable and a reference table of the results obtained by independent groups that is provided with this paper can facilitate the choice of eligible patients. A review of other pharmacological chaperones is provided as well. Frequent mutations can have residual activity as low as one-fourth of normal enzyme in vitro. The reference table with residual activity of the mutants facilitates the identification of non-pathological variants. |
| Databáze: | OpenAIRE |
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