OMIA:002065-9685 : Niemann-Pick disease, type C2 in Felis catus (domestic cat)

Categories: Lysosomal storage disease

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 601015 (gene) , 607625 (trait)

Links to relevant human diseases in MONDO:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2014

Molecular basis: Zampieri et al. (2014): "intronic mutation located 5 nt downstream of the canonical donor splice site of exon 1"; c.82+5G>A; "the mutation affects the splicing process causing the retention of 105 bp of intron 1 in the mature mRNA, which would lead to the in frame insertion of 35 amino acids between residues 28 and 29 of the NPC2 protein (p.G28_S29ins35)." Rakib et al. (2023): "studied the molecular basis of Siamese and Japanese domestic (JD) cats that were previously diagnosed with NP [Yamagami et al. 1989; Kamiya et al. 1991a; Kamiya et al. 1991b; Morozumi and Uchida 1998 ]. ... a missense mutation (NPC2:c.376G>A, p.V126M) was identified as a candidate pathogenic mutation in both types of cats. ... The Siamese cat was homozygous and the JD cat was heterozygous for this mutation. No other exonic NPC2 mutations were detected in the JD cat; however, a homozygous splice variant (c.364-4C>T) was identified, which is not known to be associated with this disease."

Clinical features: Zampieri et al. (2014) reported two kittens from the same litter "with tremors at the age of 3 months, which progressed to dystonia and severe ataxia. At 6 months of age cat 2 was unable to stand without assistance and had bilaterally reduced menace response. It died at the age of 10 months. ... At 9 months cat 1 was unable to walk, developed seizures and it was euthanized at 21 months."

Pathology: Zampieri et al. (2014): "histological analysis of the brain showed the presence of neurons with cytoplasmic swelling and vacuoles, gliosis of the substantia nigra and degeneration of the white matter. Spheroids with accumulation of ubiquitinated aggregates were prominent in the cerebellar cortex. Purkinje cells were markedly reduced in number and they showed prominent intracytoplasmic storage. Scattered perivascular aggregates of lymphocytes and microglial cells proliferation were present in the thalamus and midbrain. Proliferation of Bergmann glia was also observed. In the liver, hepatocytes were swollen because of accumulation of small vacuoles and foamy Kupffer cells were also detected. Foamy macrophages were observed within the pulmonary interstitium and alveoli as well. ... Filipin staining of cultured fibroblasts showed massive storage of unesterified cholesterol."

Breeds: Japanese domestic, Siamese (Cat) (VBO_0100221).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
NPC2 Niemann-Pick disease, type C2 Felis catus B3 NC_058373.1 (119403506..119394826) NPC2 Homologene, Ensembl , NCBI gene


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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
1572 Japanese domestic Siamese (Cat) Niemann-Pick disease, type C2 NPC2 missense Naturally occurring variant Felis_catus_9.0 B3 g.121865210G>A c.367G>A p.(V126M) XM_003987833.6; XP_003987882.1 2023 37458497
420 Niemann-Pick disease, type C2 NPC2 splicing Naturally occurring variant Felis_catus_9.0 B3 g.121872988C>T c.82+5G>A p.(G28_S29ins35) rs5334475124 2014 25396745 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002065-9685: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2023 Rakib, T.M., Islam, M.S., Uddin, M.M., Rahman, M.M., Yabuki, A., Yamagami, T., Morozumi, M., Uchida, K., Maki, S., Faruq, A.A., Yamato, O. :
Novel mutation in the feline NPC2 gene in cats with Niemann-Pick disease. Animals (Basel) 13:1744, 2023. Pubmed reference: 37458497. DOI: 10.3390/ani13111744.
2014 Zampieri, S., Bianchi, E., Cantile, C., Saleri, R., Bembi, B., Dardis, A. :
Characterization of a spontaneous novel mutation in the NPC2 gene in a cat affected by Niemann Pick type C disease. PLoS One 9:e112503, 2014. Pubmed reference: 25396745. DOI: 10.1371/journal.pone.0112503.
1998 Morozumi, M., Uchida, K. :
A case of feline lysosomal storage disease. (In Japanese) J Jpn Vet Neurol 5:21-24, 1998.
1991 Kamiya, S., Yamagami, T., Umeda, M., Sugiyama, M., Daigo, M. :
Lectin histochemistry of foamy cells in non-nervous tissues of feline sphingomyelinosis. J Comp Pathol 105:241-5, 1991. Pubmed reference: 1723414. DOI: 10.1016/s0021-9975(08)80081-3.
Kamiya, S., Yamagami, T., Umeda, M., Sugiyama, M., Daigo, M. :
Lectin histochemistry of feline sphingomyelinosis. Histol Histopathol 6:21-4, 1991. Pubmed reference: 1806052.
1989 Yamagami, T., Umeda, M., Kamiya, S., Sugiyama, K. :
Neurovisceral sphingomyelinosis in a Siamese cat. Acta Neuropathol 79:330-2, 1989. Pubmed reference: 2514553. DOI: 10.1007/BF00294670.

Edit History

  • Created by Frank Nicholas on 29 Oct 2016
  • Changed by Imke Tammen2 on 19 May 2023
  • Changed by Imke Tammen2 on 27 May 2023