Demaurex group publishes a study characterizing human mutations that cause muscular disease
The Demaurex group recently published a study entitled “ORAI1 Mutations with Distinct Channel Gating Defects in Tubular Aggregate Myopathy” in the journal “Human Mutation”, that characterizes three different mutations in ORAI1, a gene that codes for a calcium channel, that all cause a human muscular disease called tubular aggregate myopathy (TAM).
This study was a collaboration between the Demaurex group and the research group of Dr. Jocelyn Laporte from IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire, University of Strasbourg), and was jointly led by M.D.-Ph.D. student Monica Bulla-Didier, along with a postdoctoral fellow from the Laporte group. Monica used a variety of sophisticated imaging techniques, combined with electrophysiology, to show that the mutations G98S and V107M result in channels that are constantly open, while the T184M mutation only displays hyperactivity in the presence of its natural ligand STIM1. Importantly, the severity of the channel hyperactivity correlated with the clinical severity of the muscular disease in patients bearing these mutations. These results not only help us understand better the mechanisms underlying TAM, they may also one day inform the development of new therapies to alleviate this disease.