Familial distal myopathy due to PNPLA2 mutation

Mutations in the PNPLA2 gene cause the onset of Neutral Lipid Storage Disease with Myopathy (NLSD-M), a rare autosomal recessive disorder characterized by an abnormal accumulation of triacylglycerol into cytoplasmic lipid droplets (LDs). PNPLA2 codes for adipose triglyceride lipase (ATGL), an enzyme that hydrolyses fatty acids from triacylglycerol. NLSD-M patients are mainly affected by progressive myopathy, cardiomyopathy and hepatomegaly. However, their clinical severity appears to be highly variable. Here we report the clinical and genetic findings of a NLSD-M Italian family with different affected members. In our patients we identified two novel PNPLA2 missense mutations (pL56R and pI193F). All three patients had Jordan's anomaly and lipid storage in cultured fibroblasts and in muscle biopsy. Molecular and functional analysis of PNPLA2 mutations is useful to explain the variation of clinical expression of this syndrome and it might improve prognosis. This is a very interesting family since it shows heterogeneity of clinical presentation from relatively asymptomatic phenotype to full expression of a severe myopathy.