The in-frame p.Lys254del-CAPN3 deletion is not sufficient to cause late-onset camptocormia in dominantly inherited calpainopathy

Introduction/AimsLimb-girdle muscular dystrophy R1 (LGMDR1) calpain 3-related is one of the most common forms of LGMD. It is typically recessively inherited and associated with progressive weakness of proximal limb-girdle muscles. Recently, several families with an autosomal dominant inheritance transmission pattern have been reported (LGMDD4). Camptocormia is a common clinical feature in these patients. In these families, different mutations in CAPN3 have been identified, including in-frame deletions and missense mutations. In particular, two patients presenting with camptocormia carried the p.Lys254del missense mutation without a second identified mutation in CAPN3. MethodsAmong our patients, we identified two LGMDR1 families as carriers of the p.Lys254del mutation by DNA sequencing, both in homozygous and compound heterozygous states and clinically analyzed the family members carrying this mutation. ResultsInterestingly, these patients did not present the myopathic characteristics described in the so-called dominant patients. No camptocormia or any other severe clinical symptoms were observed. DiscussionAccordingly, we conclude that the p.Lys254del mutation per se cannot be solely responsible for the camptocormia observed in dominant patients. Other additional undisclosed factors might regulate the phenotype associated to a dominant inheritance pattern in CAPN3 mutation carriers.