OMIA:001962-9615 : Neuronal ceroid lipofuscinosis, 7 in Canis lupus familiaris
In other species: Japanese macaque , domestic cat
Categories: Lysosomal storage disease
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 610951 (trait) , 611124 (gene)
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: 2015
Cross-species summary: CLN7
Molecular basis: Small deletion: "c.843delT is predicted to cause a frame shift and premature stop codon resulting in a truncated protein, MFSD8:p.F282Lfs13*, missing its 239 C-terminal amino acids" in the Chinese Crested breed (Guo et al., 2015).
Faller et al. (2016) demonstrated that the same genetic variant is also present in Chihuahuas with neuronal ceroid lipofuscinosis 7.
Karli et al. (2016) reported that "the MFSD8:c.843delT variant is also present [and causal] in Chihuahuas without official registrations."
Ashwini et al. (2016) also reported the same likely causal mutation in Chihuahuas.
Clinical features: "progressive neurological decline that included blindness, anxiety, and cognitive impairment. A diagnosis of neuronal ceroid lipofuscinosis was made based on neurological signs, magnetic resonance imaging of the brain, and fluorescence microscopic and electron microscopic examination of brain sections" (Guo et al., 2015) Similar clinical signs were also observed in Chihuahuas (Faller et al. 2016).
Pathology: "Both the cerebellum and the cerebral cortex exhibited massive intracellular accumulations of autofluorescent material with a golden yellow emission under blue light illumination . . . . In the cerebellum storage material was most prominent in the Purkinje cells, but substantial amounts of this material were also present in the granular layer . . . . Perinuclear accumulations of autofluorescent storage granules were observed in neurons throughout the cerebral cortex" (Guo et al., 2015) The pathology of affected Chihuahuas was described by Faller et al. (2016).
Prevalence: Pervin et al. (2022) investigated the c.846delT allele in 1007 Chihuahuas in Japan and identified a "carrier rate of 1.29%, indicating a mutant allele frequency (0.00645)".
Breeds: Chihuahua, Chinese Crested Dog.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|MFSD8||major facilitator superfamily domain containing 8||Canis lupus familiaris||19||NC_051823.1 (12995177..13120933)||MFSD8||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|
|551||Chihuahua Chinese Crested Dog||Neuronal ceroid lipofuscinosis, 7||MFSD8||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||19||g.13010761del||c.846del||p.(F282Lfs*13)||XM_014121438.2;XP_013976913.1; published as c.843delT; coordinates in the table have been updated to a recent reference genome and / or transcript||2015||25551667||Breed and p. information obtained from Katz et al. (2017) Neurobiol Dis. doi: 10.1016/j.nbd.2017.08.017; genomic coordinates in CanFam3.1 provided by Zoe Shmidt and Robert Kuhn.|
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.
|2022||Pervin, S., Islam, M.S., Tada, N., Tsutsui, T., Rahman, M.M., Yabuki, A., Tacharina, M.R., Rakib, T.M., Maki, S., Yamato, O. :|
|Screening and carrier rate of neuronal ceroid lipofuscinosis in Chihuahua dogs in Japan. Animals (Basel) 12:1210, 2022. Pubmed reference: 35565635 . DOI: 10.3390/ani12091210.|
|2021||Cerda-Gonzalez, S., Packer, R.A., Garosi, L., Lowrie, M., Mandigers, P.J.J., O'Brien, D.P., Volk, H.A. :|
|International veterinary canine dyskinesia task force ECVN consensus statement: Terminology and classification. J Vet Intern Med 35:1218-1230, 2021. Pubmed reference: 33769611 . DOI: 10.1111/jvim.16108.|
|2020||Story, B.D., Miller, M.E., Bradbury, A.M., Million, E.D., Duan, D., Taghian, T., Faissler, D., Fernau, D., Beecy, S.J., Gray-Edwards, H.L. :|
|Canine models of inherited musculoskeletal and neurodegenerative diseases. Front Vet Sci 7:80, 2020. Pubmed reference: 32219101 . DOI: 10.3389/fvets.2020.00080.|
|2017||Katz, M.L., Rustad, E., Robinson, G.O., Whiting, R.E.H., Student, J.T., Coates, J.R., Narfstrom, K. :|
|Canine neuronal ceroid lipofuscinoses: Promising models for preclinical testing of therapeutic interventions. Neurobiol Dis 108:277-87, 2017. Pubmed reference: 28860089 . DOI: 10.1016/j.nbd.2017.08.017.|
|2016||Ashwini, A., D'Angelo, A., Yamato, O., Giordano, C., Cagnotti, G., Harcourt-Brown, T., Mhlanga-Mutangadura, T., Guo, J., Johnson, G.S., Katz, M.L. :|
|Neuronal ceroid lipofuscinosis associated with an MFSD8 mutation in Chihuahuas. Mol Genet Metab 118:326-32, 2016. Pubmed reference: 27211611 . DOI: 10.1016/j.ymgme.2016.05.008.|
|Faller, K.M., Bras, J., Sharpe, S.J., Anderson, G.W., Darwent, L., Kun-Rodrigues, C., Alroy, J., Penderis, J., Mole, S.E., Gutierrez-Quintana, R., Guerreiro, R.J. :|
|The Chihuahua dog: A new animal model for neuronal ceroid lipofuscinosis CLN7 disease? J Neurosci Res 94:339-47, 2016. Pubmed reference: 26762174 . DOI: 10.1002/jnr.23710.|
|Karli, P., Oevermann, A., Bauer, A., Jagannathan, V., Leeb, T. :|
|MFSD8 single-base pair deletion in a Chihuahua with neuronal ceroid lipofuscinosis. Anim Genet :, 2016. Pubmed reference: 27145727 . DOI: 10.1111/age.12449.|
|2015||Guo, J., O'Brien, D.P., Mhlanga-Mutangadura, T., Olby, N.J., Taylor, J.F., Schnabel, R.D., Katz, M.L., Johnson, G.S. :|
|A rare homozygous MFSD8 single-base-pair deletion and frameshift in the whole genome sequence of a Chinese Crested dog with neuronal ceroid lipofuscinosis. BMC Vet Res 10:960, 2015. Pubmed reference: 25551667 . DOI: 10.1186/s12917-014-0181-z.|
- Created by Frank Nicholas on 02 May 2015
- Changed by Tosso Leeb on 01 Apr 2016
- Changed by Frank Nicholas on 13 May 2016
- Changed by Frank Nicholas on 25 May 2016
- Changed by Imke Tammen2 on 10 Jan 2023