التفاصيل البيبلوغرافية
| العنوان: |
Unbalanced GLA mRNAs ratio quantified by real-time PCR in Fabry patients' fibroblasts results in Fabry disease. |
| المؤلفون: |
Filoni, Camilla, Caciotti, Anna, Carraresi, Laura, Donati, Maria Alice, Mignani, Renzo, Parini, Rossella, Filocamo, Mirella, Soliani, Fausto, Simi, Lisa, Guerrini, Renzo, Zammarchi, Enrico, Morrone, Amelia |
| المصدر: |
European Journal of Human Genetics; Nov2008, Vol. 16 Issue 11, p1311-1317, 7p, 2 Black and White Photographs, 1 Diagram, 2 Charts, 3 Graphs |
| مصطلحات موضوعية: |
HUMAN genetics, GENETIC mutation, MESSENGER RNA, HYDROLASES, GLYCOSPHINGOLIPIDS |
| مستخلص: |
Total or partial deficiency of the human lysosomal hydrolase α-galactosidase A is responsible for Fabry disease, the X-linked inborn error of glycosphingolipid metabolism. Together with the predominant α-galactosidase A gene mRNA product encoding the lysosomal enzyme, a weakly regulated alternatively spliced α-galactosidase A transcript is expressed in normal tissues, but its overexpression, due to the intronic g.9331G>A mutation, leads to the cardiac variant. We report the molecular characterization of five Fabry patients including two siblings. Sequencing analysis of the α-galactosidase A gene coding region and intron/exon boundaries identified the new c.124A>G (p.M42V) genetic lesion as well as a known deletion in three patients, whereas in the two remaining patients, no mutations were identified. To evaluate possible α-galactosidase A gene transcription alterations, both predominant and alternatively spliced mRNAs were quantified by absolute real-time PCR on total RNA preparations from the patients' fibroblasts. An impressive reduction in the predominant α-galactosidase A transcript was detected in the last patients (Pt 4 and Pt 5). However, the alternatively spliced mRNA was dramatically overexpressed in one of them, carrying a new intronic lesion (g.9273C>T). These findings strongly suggest a correlation between this new intronic mutation and the unbalanced α-galactosidase A mRNAs ratio, which could therefore be responsible for the reduced enzyme activity causing Fabry disease. The real-time assay developed here to investigate the two α-galactosidase A mRNAs might play a crucial role in revealing possible genetic lesions and in confirming the pathogenetic mechanisms underlying Fabry disease.European Journal of Human Genetics (2008) 16, 1311–1317; doi:10.1038/ejhg.2008.109; published online 18 June 2008 [ABSTRACT FROM AUTHOR] |
|
Copyright of European Journal of Human Genetics is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder