Journal of Genetic Syndromes & Gene Therapy
Open Access

Abstract

Fourty-Four Years of Brody Disease: It is Time to Review

Guglielmi V, Voermans NC, Gualandi F, Van Engelen BG, Ferlini A, Tomelleri G and Vattemi G

Brody disease is an inherited skeletal muscle disorder clinically characterized by exercise-induced muscle stiffness and delayed relaxation due to a diminished sarcoplasmic reticulum Ca2+-ATPase activity. The disease is transmitted as an autosomal recessive trait and results from mutations in the ATP2A1 gene encoding the sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (SERCA1), a protein that catalyzes the ATP-dependent Ca2+ uptake from the cytosol to the lumen of sarcoplasmic reticulum. Mutations in the SERCA1-encoding gene are absent in a quote of patients with autosomal recessive pattern and have never been found in patients with an autosomal dominant inheritance suggesting the genetic heterogeneity of the disease. Therefore, the term Brody syndrome has been proposed to designate patients with decreased sarcoplasmic reticulum Ca2+-ATPase activity but without ATP2A1 mutation. The review aims to summarize the salient clinical, laboratory and biochemical findings in patients with Brody disease and Brody syndrome.