OMIA 001962-9685 : Neuronal ceroid lipofuscinosis, 7 in Felis catus

In other species: Japanese macaque , dog

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

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2019

Cross-species summary: CLN7

Molecular basis: "Whole‐genome sequencing of the affected cat with filtering of variants against a database of unaffected cats" enabled Guevar et al. (2019) to identify "Two homozygous private (unique to individual or families and therefore absent from the breed‐matched controlled population) protein‐changing variants in the major facilitator superfamily domain 8 (MFSD8) gene, a known candidate gene for neuronal ceroid lipofuscinosis type 7 (CLN7), were identified [c.19G>C; p.(Asp7His) and c.780delT; p.(Gln262Lysfs*33)]. The affected cat was homozygous for the alternative allele at both variants." The two variants were in complete disequilibrium in the 1 affected and 141 unaffected cats surveyed. The authors concluded that of the two variants, the frameshift variant was more likely to be pathogenic because it "most likely leads to a complete loss of function of the MFSD8 gene".

Clinical features: Guevar et al. (2019): "A 2‐year‐old male domestic shorthair cat was presented for a progressive history of abnormal posture, behavior, and mentation. Menace response was absent bilaterally, and generalized tremors were identified on neurological examination. A neuroanatomical diagnosis of diffuse brain dysfunction was made. A neurodegenerative disorder was suspected. Magnetic resonance imaging findings further supported the clinical suspicion."

Breed: Domestic Shorthair.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MFSD8 major facilitator superfamily domain containing 8 Felis catus B1 NC_018726.3 (98898000..98959444) MFSD8 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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.

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
Domestic Shorthair Neuronal ceroid lipofuscinosis, 7 MFSD8 deletion, small (<=20) Felis_catus_9.0 B1 c.780delT p.(Q262LKfs*33) Guevar et al. (2019): "XM_019828986.2:c.780delT or XP_019684545.1:p.(Gln262Lysfs*33)" 2020 31860737

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.
2020 Guevar, J., Hug, P., Giebels, F., Durand, A., Jagannathan, V., Leeb, T. :
A major facilitator superfamily domain 8 frameshift variant in a cat with suspected neuronal ceroid lipofuscinosis. J Vet Intern Med 34:289-293, 2020. Pubmed reference: 31860737. DOI: 10.1111/jvim.15663.
Lyons, L.A. :
Precision medicine in cats-The right biomedical model may not be the mouse! PLoS Genet 16:e1009177, 2020. Pubmed reference: 33290388. DOI: 10.1371/journal.pgen.1009177.

Edit History


  • Created by Frank Nicholas on 28 Jan 2020
  • Changed by Frank Nicholas on 28 Jan 2020