Molecular Genetics of Niemann-Pick Type C Disease in Italy: An Update on 105 Patients and Description of 18 Novel Variants

Niemann-Pick type C (NPC) disease is an autosomal recessive lysosomal storage disorder caused by mutations in or genes. In 2009, the molecular characterization of 44 NPC Italian patients has been published. Here, we present an update of the genetic findings in 105 Italian NPC patients belonging to 83 unrelated families (77 NPC1 and 6 NPC2). and genes were studied following an algorithm recently published. Eighty-four different and five alleles were identified. Only two alleles remained non detected. Sixty-two percent of alleles were due to missense variants. The most frequent mutation was the p.F284Lfs*26 (5.8% of the alleles). All mutations were found in the homozygous state, and all but one was severe. Among newly diagnosed patients, 18 novel mutations were identified. The pathogenic nature of 7/9 missense alleles and 3/4 intronic variants was confirmed by filipin staining and NPC1 protein analysis or mRNA expression in patient's fibroblasts. Taken together, our previous published data and new results provide an overall picture of the molecular characteristics of NPC patients diagnosed so far in Italy.