OMIA 000938-9615 : Spinal dysraphism in Canis lupus familiaris

In other species: cattle

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2013

Mapping: In a GWAS on just 4 unrelated affected Weimaraners and 96 controls from the same breed were each genotyped with the Illumina 170K CanineHD BeadChip (yielding 114,775 informative SNPs for analysis), Safra et al. (2013) used GWAS to identified a 1.5Mb candidate region on chromosome CFA8 that includes 18 genes.

Molecular basis: By sequencing the most likely of the genes (based on clinical signs in mice that are mutant for this gene) in the candidate region on CFA8, namely NKX2-8, Safra et al. (2013) identified a causal mutation as "a G to AA frameshift mutation within exon 2 of the gene, resulting in a premature stop codon that is predicted to produce a truncated protein" (p.A150VfsX1). Importantly, Safra et al. (2013) then sequenced the "exons of NKX2-8 . . . in human patients with spina bifida and rare variants (rs61755040 and rs10135525) were found to be significantly over-represented (p = 0.036). This is the first documentation of a potential role for NKX2-8 in the etiology of [human] NTDs, made possible by investigating the molecular basis of naturally occurring mutations in dogs."

Breed: Weimaraner.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
NKX2-8 NK2 homeobox 8 Canis lupus familiaris 8 NC_006590.3 (15151884..15149318) NKX2-8 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
Weimaraner Spinal dysraphism NKX2-8 indel, small (<=20) p.A150VfsX1 2013 23874236

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.
2013 Safra, N., Bassuk, A.G., Ferguson, P.J., Aguilar, M., Coulson, R.L., Thomas, N., Hitchens, P.L., Dickinson, P.J., Vernau, K.M., Wolf, Z.T., Bannasch, D.L. :
Genome-wide association mapping in dogs enables identification of the homeobox gene, NKX2-8, as a genetic component of neural tube defects in humans. PLoS Genet 9:e1003646, 2013. Pubmed reference: 23874236. DOI: 10.1371/journal.pgen.1003646.
2012 Allett, B., Broome, M.R., Hager, D. :
MRI of a split cord malformation in a German shepherd dog. J Am Anim Hosp Assoc 48:344-51, 2012. Pubmed reference: 22843830. DOI: 10.5326/JAAHA-MS-5780.
1995 Ruberte, J., AƱor, S., Carretero, A., Vilafranca, M., Navarro, M., Mascort, J., Pumarola, M. :
Malformations of the vertebral bodies and the ribs associated to spinal dysraphism without spina bifida in a Pekingese dog. Zentralbl Veterinarmed A 42:307-13, 1995. Pubmed reference: 8578905.
1992 Bailey, C.S., Morgan, J.P. :
Congenital spinal malformations. Vet Clin North Am Small Anim Pract 22:985-1015, 1992. Pubmed reference: 1641930.
1991 Vandenbroek, A.H.M., Else, R.W., Abercromby, R., France, M. :
Spinal Dysraphism in the Weimaraner Journal of Small Animal Practice 32:258-260, 1991.
1982 Engel, H.N., Draper, D.D. :
Comparative prenatal development of the spinal cord in normal and dysraphic dogs: fetal stage. Am J Vet Res 43:1735-43, 1982. Pubmed reference: 6756222.
Engel, H.N., Draper, D.D. :
Comparative prenatal development of the spinal cord in normal and dysraphic dogs: embryonic stage. Am J Vet Res 43:1729-34, 1982. Pubmed reference: 6756221.
1976 Draper, D.D., Kluge, J.P., Millerw, J. :
Clinical and pathological aspects of spinal dysraphism in dogs. Thessaloniki 1:134-137, 1976.
1974 Neufeld, J.L., Little, P.B. :
Spinal dysraphism in a Dalmatian dog. Can Vet J 15:335-6, 1974. Pubmed reference: 4434313.
1973 Klaus, B. :
[Picture report. Spinal dysraphism in a German shepherd]. Berl Munch Tierarztl Wochenschr 86:95, 1973. Pubmed reference: 4732250.
1972 Confer, A.W., Ward, B.C. :
Spinal dysraphism: a congenital myelodysplasia in the Weimaraner Journal of the American Veterinary Medical Association 160:1423-1426, 1972. Pubmed reference: 5023160.
1967 Geib, L.W., Bistner, S.I. :
Spinal cord dysraphism in a dog. J Am Vet Med Assoc 150:618-20, 1967. Pubmed reference: 5339905.
1965 Foster, S.J. :
A case of sternal dysraphism and two cases of suspected congenital diaphragmatic hernia in the dog. Vet Rec 77:1112-4, 1965. Pubmed reference: 5318050.
McGrath, J.T. :
Spinal dysraphism in the dog, with comments on syringomylia Pathologia Veterinaria 2:1-36 (Supplement), 1965. Pubmed reference: 5893238.

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  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Frank Nicholas on 19 Aug 2013