Brody Disease: Insights Into Biochemical Features of SERCA1 and Identification of a Novel Mutation

• DOI: 10.1097/nen.0b013e3181d0f7d5
• Publication Date: 2010-02-19T03:17:05Z
• Authors: Gaetano Vattemi; Francesca Gualandi; Arie Oosterhof; Matteo Marini; Paola Tonin; Paola Rimessi; Marcella Neri; Valeria Guglielmi; Anna Russignan; Consuelo Poli; Toin H. van Kuppe...; Alessandra Ferlini; Giuliano Tomelleri
• Keywords: Sarcoplasm

Brody disease is an inherited disorder of skeletal muscle function characterized by increasing impairment relaxation during exercise. The autosomal recessive form can be caused mutations in the ATP2A1 gene, which encodes for sarcoplasmic/endoplasmic reticulum Ca-ATPase 1 (SERCA1) protein. We studied 2 siblings affected disease. patients complained exercise-induced delay and stiffness since childhood had gene analysis ATP2A1. Morphologic biochemical studies were performed on a biopsy from patient. showed fiber size variation increased numbers fibers with internal nuclei. Ultrastructural examination revealed dilatation lateral cisternae proliferation tubular elements sarcoplasmic reticulum. By immunohistochemistry, SERCA1 was expressed normal pattern, but activity significantly reduced. Immunoblotting after high-resolution 2-dimensional gel electrophoresis significant difference amount protein between patient controls. Both found to have previously unreported in-frame deletions Because has specific characteristics our patient, these results underline importance pathologic analyses diagnosis. In addition, we describe novel gene.