OMIA 001962-9615 : Neuronal ceroid lipofuscinosis, 7 in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 610951

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2015

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).

Breeds: Chihuahua, Chinese Crested Dog.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MFSD8 major facilitator superfamily domain containing 8 Canis lupus familiaris 19 NC_006601.3 (12905336..13030901) MFSD8 Homologene, Ensembl, NCBI gene

Variants

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Chihuahua Chinese Crested Dog Neuronal ceroid lipofuscinosis, 7 MFSD8 deletion, small (<=20) c.843delT p.F282Lfs*13 2015 25551667 Breed and p. information obtained from Katz et al. (2017) Neurobiol Dis. doi: 10.1016/j.nbd.2017.08.017

References


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.
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 :, 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.

Edit History


  • 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