From clinical to molecular diagnosis: relevance of the MLPA in one case of recessive myotonia congenita – case report

Abstract Background: Myotonia congenita (MC) is traditionally classified as Thomsen (autosomal dominant) and Becker (autosomal recessive) diseases, caused by mutations in the CLCN1, encoding the skeletal muscle voltage-gated chloride channel (ClC-1). MC is clinically characterized by muscle stiffness at the beginning of exercise (i.e. myotonia), alleviated by repetition of contraction (ie. warm-up effect). Case presentation:We report here an Italian patient affected by diffuse muscle hypertrophy, predominant in lower limb, neck, and trapezius and difficulty in getting up from a chair after prolonged rest, suggestive of recessive MC. The combination of a specific next-generation sequencing panel for skeletal muscle channelopathies and multiplex ligation-dependent probe amplification for CLCN1gene, leaded to patient’s molecular characterization with the detection of the known p.G482R mutation and a novel deletion of the last 3 exons [c.(2403+1_2404-1)_*39del]. Conclusions: This report demonstrates the importance of combining multiple genetic techniques to define recessive forms of MC.