Mutations in ATP6V1E1 or ATP6V1A Cause Autosomal-Recessive Cutis Laxa.

ABSTRACT: Defects of the V-type proton (H⁺) ATPase (V-ATPase) impair acidification and intracellular trafficking of membrane-enclosed compartments, including secretory granules, endosomes, and lysosomes. Whole-exome sequencing in five families affected by mild to severe cutis laxa, dysmorphic facial features, and cardiopulmonary involvement identified biallelic missense mutations in ATP6V1E1 and ATP6V1A, which encode the E1 and A subunits, respectively, of the V₁ domain of the heteromultimeric V-ATPase complex. Structural modeling indicated that all substitutions affect critical residues and inter- or intrasubunit interactions. Furthermore, complexome profiling, a method combining blue-native gel electrophoresis and liquid chromatography tandem mass spectrometry, showed that th

SUBMITTER: Van Damme T 

PROVIDER: S-EPMC5294668 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature