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

In other species: domestic cat , sheep

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 612768 (gene)

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"

Clinical features: Affected animals present with generalised tremors at about 2 to 3 weeks of age (Kornegay et al., 1987; Pemberton et al., 2014). Clinical signs gradually resolve in most dogs by 3 to 4 months of age (Kornegay et al., 1987; Pemberton et al., 2014), "though some dogs retained a persistent fine tremor of the hind limbs" (Pemberton et al., 2014). Pemberton et al. (2014) suggest that hyppomyelination previously described in Chow Chow dogs (Vandevelde and Braund, 1981; Vandevelde et al., 1978) is identical to the disease in Weimaraner dogs.

Pathology: Kornegay et al., (1987) "Many axons in the brain and spinal cord were either thinly myelinated or nonmyelinated in the affected dogs relative to the controls, while the peripheral nervous system was normally myelinated. The degree of hypomyelination seemed particularly severe at the periphery of the lateral and ventral funiculi of the spinal cord. In all areas of white matter evaluated, astrocytes subjectively outnumbered oligodendrocytes in the [affeted] Weimaraners ..."

Associated gene:

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


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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 Year Published PubMed ID(s) Acknowledgements
531 Weimaraner (Dog) 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

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:000526-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset].


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.
1981 Vandevelde, M., Braund, K.G., Luttgen, P.J., Higgins, R.J. :
Dysmyelination in Chow Chow dogs: further studies in older dogs. Acta Neuropathol 55:81-7, 1981. Pubmed reference: 7315204. DOI: 10.1007/BF00699232.
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
  • Changed by Imke Tammen2 on 13 Jun 2023