OMIA:002065-9685 : Niemann-Pick disease, type C2 in Felis catus
Categories: Lysosomal storage disease
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 601015 (gene) , 607625 (trait)
Links to MONDO diseases:
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).
|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||Inferred EVA rsID||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||Reference not in PubMed; see OMIA 002065-9685 for reference details|
|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)||2014||25396745||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool|
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 13:Article:1744, 2023. DOI: doi.org/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.|
- Created by Frank Nicholas on 29 Oct 2016
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- Changed by Imke Tammen2 on 27 May 2023