New VMD2 gene mutations identified in patients affected by Best vitelliform macular dystrophy
Résumé
The VMD2 gene encodes a transmembrane protein named bestrophin-1 which is a Ca 2+-sensitive chloride channel. Here, we identified six new VMD2 mutations in patients with Best's macular dystrophy. One of these mutations (Q293H) is particularly severe. Patch clamp analysis of HEK cells expressing the Q293H mutant shows that this mutant channel is non-functional. Furthermore, the Q293H mutant inhibits the function of wild-type bestrophin-1 channels in a dominant negative manner. Direct sequencing analysis of the 11 VMD2 exons revealed new abnormal profiles in exons 4, 6 and 8 due to mono-allelic transitions and transversions. We also detected five frequent pathogenic sequence changes that have been previously reported and annotated in an online database.
Domaines
Sciences du Vivant [q-bio]Origine | Fichiers produits par l'(les) auteur(s) |
---|