We identified loss-of-function mutations in ATP6V0A2, encoding the a2 subunit of the V-type H+ ATPase, in several families with autosomal recessive cutis laxa type II or wrinkly skin syndrome. The mutations result in abnormal glycosylation of serum proteins (CDG-II) and cause an impairment of Golgi trafficking in fibroblasts from affected individuals. These results indicate that the a2 subunit of the proton pump has an important role in Golgi function.
Bibliographical noteFunding Information:
We thank W. Morelle for the MALDI-TOF glycan analysis, J. Jaeken and H. Carchon for the capillary zone electrophoresis, and C. Schlack for her brilliant technical assistance. This work was supported by Bundesministerium für Bildung und Forschung (BMBF) grant 01GM0623 and a grant from the Deutsche Forschungsgemeinschaft to UK, by the VIB (to E.R. and W.A.), by the Fonds Wetenschappelijk Onderzoek-Vlaanderen (grants G.0504.06 and G.0173.04 to W.A. and G.M., respectively) and by the Sixth Framework program of the European Union (Euroglycanet: LSHM-2005-512131). E.R. holds an Instituut voor de aanmoediging van innovatie door wetenschap en technologie in Vlaanderen (IWT) doctoral fellowship.