Activating mutations in STIM1 and ORAI1 cause overlapping syndromes of tubular myopathy and congenital miosis.

ABSTRACT: Signaling through the store-operated Ca(2+) release-activated Ca(2+) (CRAC) channel regulates critical cellular functions, including gene expression, cell growth and differentiation, and Ca(2+) homeostasis. Loss-of-function mutations in the CRAC channel pore-forming protein ORAI1 or the Ca(2+) sensing protein stromal interaction molecule 1 (STIM1) result in severe immune dysfunction and nonprogressive myopathy. Here, we identify gain-of-function mutations in the cytoplasmic domain of STIM1 (p.R304W) associated with thrombocytopenia, bleeding diathesis, miosis, and tubular myopathy in patients with Stormorken syndrome, and in ORAI1 (p.P245L), associated with a Stormorken-like syndrome of congenital miosis and tubular aggregate myopathy but without hematological abnormalities. Heterologous e

SUBMITTER: Nesin V 

PROVIDER: S-EPMC3964084 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature