NPC is inherited in an autosomal recessive manner, i.e., two copies of a gene mutation at a particular locus on one of the 22 pairs of autosomes (non-sex chromosomes) must be present for the disease phenotype to manifest. The phenotype of a particular inherited mutation (i.e., age of onset and profile/severity of symptoms) usually runs consistently within families1.
In each pregnancy of a carrier couple, there is a 25% chance that they will both pass their non-functional mutant NPC genes to a child, who would then be affected. There is a 50% chance that only one of them would pass a non-functional gene, making the child a heterozygote carrier like the parents. There is a 25% chance that both functional genes would be passed and the child would neither be a carrier nor affected. Overall, unaffected children have a two in three risk of carrying one abnormal NPC1 or NPC2 allele. Further, each sibling of an affected individual’s parents is at a 50% risk of being a carrier.
Reference:
1. Imrie J, Dasgupta S, Besley GT et al. The natural history of Niemann–Pick disease type C in the UK. J Inherit Metab Dis 2007;30:51–9.
© 2007 Blackwell Publishing Limited. Reproduced by permission.