RYR1 mutation screening 1992 – 2014: a genetic report on 22 years from the Würzburg MH unit

Abstract

Materials and methods In 1992, we began to screen MHS individual by PCR and restriction enzyme digestion for the few then known RYR1 mutations. At around 1995, we switched to Sanger sequencing of selected exons (mutation hot-spots) and for a number of years, we analysed five exons in MHS (exons 17, 39, 40, 45, 46) and four in myopathic subjects (exons 95, 100, 101, 102). From 2002 on, we also included whole-gene sequencing of all 106 exons by Sanger or NGS technologies (starting from 2011). In total, we have screened 1.029 unrelated index cases. The great majority of malignant hyperthermia (MH) individuals had a positive in vitro contracture test (IVCT) result (MHS or MH equivocal (MHE)) or a likely clinical MH episode. Patients with congenital myopathies were referred on the basis of their clinical presentation.