COMPOSITIONS AND METHODS FOR DIAGNOSIS OF AUTOPHAGIC VACUOLAR MYOPATHY

摘要

Transmembrane V-ATPase proton pump complexes regulate pH of extracellular space or intracellular compartments of cells. V-ATPase complexes are ubiquitous in cells across species. A human orthologue of yeast vma21, LOC203547 (VMA21), is likely involved in the assembly of the V-ATPase. Hypomorphic mutations of VMA21 are identified from XMEA patients. Methods to diagnose and/or distinguish between different forms of vacuolar or vacuolated myopathy in an individual or patient are provided based either on the sequence of the VMA21 gene and/or the level and/or activity of the V-ATPase complex. Compositions of the present invention may comprise DNA, RNA, or protein molecules corresponding to all or a portion of VMA21 and including one or more of the mutations in VMA21 identified. Cultured cells or cell lines having one or more mutations in the VMA21 gene derived from patients having a form of vacuolar or vacuolated myopathy are provided.