Niemann-Pick type C disease: a novel NPC1 mutation segregating in a Greek island

Niemann-Pick type C (NPC) disease is a rare autosomal recessive lysosomal storage disease, exhibiting an extremely heterogeneous clinical phenotype. It is a cellular lipid trafficking disorder characterized by the accumulation in the lysosomal/late endosomal system of a variety of lipids, especially unesterified cholesterol. So far two genes, NPC1 or NPC2, have been linked to the disorder. It is a panethnic disease for which two isolates have been described. We present a novel NPC1 mutation (p.A1132P; c.3394G>C) identified in homozygosity in two patients originating from the same small town of an Aegean Sea island and the results of the broad screening of their extended families. Overall 153 individuals have so far been investigated and a total of 64 carriers were identified. Moreover a common descent of the individuals tested was revealed and all carriers could be traced back to a common surname, apparently originating from a common ancestor couple six generations back. The mutation was found associated with an uncommon haplotype in the island that is also present in other populations.