OMIA 000526-9615 : Hypomyelination of the central nervous system in Canis lupus familiaris

In other species: domestic cat

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"

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
FNIP2 folliculin interacting protein 2 Canis lupus familiaris 15 NC_006597.3 (55871782..55962676) FNIP2 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
Weimaraner Hypomyelination of the central nervous system FNIP2 deletion, small (<=20) c.880delA, XM_532705 p.Ile294fsX296 2014 24272703

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.
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.

Edit History


  • Created by Frank Nicholas on 02 Nov 2010
  • Changed by Frank Nicholas on 27 Nov 2013