Niemann-Pick disease (NP) type C is an autosomal, recessive, and inherited neurovisceral genetic disorder characterized by the accumulation of unesterified cholesterol and glycolipids in cellular lysosomes and late endosomes, with a wide spectrum of clinical phenotypes. This study aimed to determine the molecular genetic alterations in two cases of felines with NP in Japan, a Siamese cat in 1989 and a Japanese domestic (JD) cat in 1998. Sanger sequencing was performed on 25 exons of the feline NPC1 gene and 4 exons of the feline NPC2 gene, using genomic DNA extracted from paraffin-embedded tissue specimens. The sequenced exons were compared with reference sequences retrieved from the GenBank database. The identified mutations and alterations were then analyzed using different prediction algorithms. No pathogenic mutations were found in feline NPC1; however, c.376G>A (p.V126M) was identified as a pathogenic mutation in the NPC2 gene. The Siamese cat was found to be homozygous for this mutation. The JD cat was heterozygous for the same mutation, but no other exonic NPC2 mutation was found. Furthermore, the JD cat had a homozygous splice variant (c.364-4C>T) in the NPC2 gene, which is not known to be associated with this disease. The NPC2:c.376G>A (p.V126M) mutation is the second reported pathogenic mutation in the feline NPC2 gene that may be present in the Japanese cat population.
Keywords: Japanese domestic cat; Niemann–Pick disease type C; Siamese cat; feline NPC2 gene; lysosomal storage disease.