Two patients with G MPPB mutation: The overlapping phenotypes of limb‐girdle myasthenic syndrome and limb‐girdle muscular dystrophy dystroglycanopathy

Mutations in the guanosine diphosphate–mannose pyrophosphorylase‐B gene ( GMPPB ) have been identified in congenital muscular dystrophies, limb‐girdle muscular dystrophy (LGMD2T), and congenital myasthenic syndromes (CMSs); overall, 41 patients have been described. Methods Two patients presented with a myasthenic syndrome (patient 1; 74 years old) and rhabdomyolysis (patient 2; 23 years old). Examinations included repetitive nerve stimulation, muscle biopsy and whole‐body MRI (WBMRI); next generation sequencing facilitated diagnosis. Results We identified the following GMPPB mutations: c.79G>C/c.859C>T in the 23‐year‐old man with LGMD2T‐phenotype and c.79G>C homozygosity in the 74‐year‐old woman with CMS phenotype. WBMRI showed fatty degeneration of paraspinal, thigh adductor, and calf muscles in patient 1 and edematous changes of the soleus muscle in patient 2. Conclusions This case of c.79G>C homozygosity causing a mild, late‐onset CMS phenotype, confirms the mild nature of this common mutation. The descriptions of these 2 new GMPPB cases add to the knowledge regarding this recently discovered, heterogeneous disease. Muscle Nerve 56 : 334–340, 2017