OMIA 000526-9615 : Hypomyelination of the central nervous system in Canis lupus familiaris
Category: Nervous system phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 612768 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2014
Mapping: By conducting a GWAS on 84 Weimaraner dogs "(40 males and 44 females) of whom 14 were affecteds, 19 were known carriers, and 51 were unaffecteds", each genotyped with the Illumina CanineHD BeadChip (yielding 95,990 informative autosomal SNPs), Pemberton et al. (2014) mapped this disorder to a 5Mb region (57.3 to 62.3) on chromosome CFA15. Subsequent homozygosity mapping narrowed this to a 3.7Mb region (573. to 61.0).
Molecular basis: After sequencing the most obvious candidate gene in the candidate region (see Mapping section) and discovering no mutations, Pemberton et al. (2014) sequenced all 199 exons of the remaining 16 genes in that region, yielding 54 variants, only one of which had the potential to be deleterious. This variant turned out to be the causal mutation: "a deletion of a single A nucleotide within exon 9 of the gene encoding folliculin-interacting protein 2 (FNIP2). This mutation at nucleotide 880 of the coding sequence (c.880delA, XM_532705) causes a frameshift, and the amino acid sequence is altered beginning at codon 294, with a premature translation stop signal introduced at codon 296 . . . . A highly truncated protein of 295 amino acids compared with the wild-type protein of 1,106 amino acids is predicted to result from this p.Ile294fsX296 mutation"
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|FNIP2||folliculin interacting protein 2||Canis lupus familiaris||15||NC_051819.1 (56573299..56706386)||FNIP2||Homologene, Ensembl, NCBI gene|
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.
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|
|531||Weimaraner||Hypomyelination of the central nervous system||FNIP2||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||15||g.55928287del||c.1078del||p.(I360Lfs*3)||XM_005629382.3; XP_005629439.1; published as CanFam2:58974928delA, XM_532705:c.880delA and p.(I294fs*296) - coordinates in the table have been updated to a recent reference genome and / or transcript and HGVS nomenclature||2014||24272703|
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.
|2014||Pemberton, T.J., Choi, S., Mayer, J.A., Li, F.Y., Gokey, N., Svaren, J., Safra, N., Bannasch, D.L., Sullivan, K., Breuhaus, B., Patel, P.I., Duncan, I.D. :|
|A mutation in the canine gene encoding folliculin-interacting protein 2 (FNIP2) associated with a unique disruption in spinal cord myelination. Glia 62:39-51, 2014. Pubmed reference: 24272703. DOI: 10.1002/glia.22582.|
|2010||Millán, Y., Mascort, J., Blanco, A., Costa, C., Masian, D., Guil-Luna, S., Pumarola, M., Martin de Las Mulas, J. :|
|Hypomyelination in three Weimaraner dogs. J Small Anim Pract 51:594-8, 2010. Pubmed reference: 20973788. DOI: 10.1111/j.1748-5827.2010.00997.x.|
|1988||Comont, P.S.V., Palmer, A.C., Williams, A.E. :|
|Weakness associated with spinal subpial myelopathy in a Weimaraner puppy. Journal of Small Animal Practice 29:367–372, 1988.|
|1987||Kornegay, JN., Goodwin, MA., Spyridakis, LK. :|
|Hypomyelination in Weimaraner dogs. Acta Neuropathol 72:394-401, 1987. Pubmed reference: 3577694.|
|1978||Amassian, V.E., Eberle, L., Rudell, A. :|
|Mode of cerebellar functioning in contact placing in kittens [proceedings]. J Physiol 284:179P-180P, 1978. Pubmed reference: 731520.|
|Vandevelde, M., Braund, K.G., Walker, T.L., Kornegay, J.N. :|
|Dysmyelination of the central nervous system in the Chow-Chow dog. Acta Neuropathol 42:211-5, 1978. Pubmed reference: 676669.|
- Created by Frank Nicholas on 02 Nov 2010
- Changed by Frank Nicholas on 27 Nov 2013