OMIA:001788-9615 : Leukoencephalomyelopathy in Canis lupus familiaris |
Categories: Nervous system phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 612334 (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: 2018
Species-specific symbol: LEMP
Mapping: A GWAS involving 44 affected and 186 normal Leonbergers, each genotyped with the 170K the Illumina CanineHD BeadChip array (yielding 112,833 informative SNPs), followed by haplotype analysis, enabled Minor et al. (2018) to map this disorder to a region of chromosome CFA18 from 16.6Mb to 19.9 Mb.
Molecular basis: Noting the similarity of this disorder with leukoencephalopathy with brain stem and spinal cord involvement and elevated lactate levels in humans, which is caused by mutations in DARS2 [see OMIM 611105], Hirschvogel et al. (2013) adopted the comparative candidate gene strategy and sequenced the DARS2 gene in an affected Rottweiler, but were unable to find a causal mutation.
Whole genome resequencing of an affected Leonberger revealed to Minor et al. (2018) that "Only a single variant (chr18:g.16987520 G>C) [c.538 G>C; p.Ala180Pro] was predicted to affect the coding sequence of an annotated gene" in the candidate region on CFA18. The authors then reported that "Sanger sequencing confirmed the presence of this variant . . . and its nearly perfect association to the LEMP phenotype". Providing further evidence of the imperfect association, Minor et al. (2018) reported "approximately 1% (6/574) of non-affected [Leonberger] dogs at eight years of age were homozygous for the mutant allele, indicating reduced penetrance".
The same authors identified a different likely causal variant in Rottweilers, namely g.16987327_16987328insC; c.345_346insC; p.Glu116ArgfsTer186. They also reported that "Haplotype analysis of SNP array genotypes revealed that the frameshift variant was present in diverse haplotypes in Rottweilers, and also in Great Danes, indicating an old origin of this second NAPEPLD variant".
Breeds: Afghan Hound, Dutch Kooiker, Leonberger, Rottweiler.
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| NAPEPLD | N-acyl phosphatidylethanolamine phospholipase D | Canis lupus familiaris | 18 | NC_051822.1 (17253389..17307355) | NAPEPLD | Homologene, Ensembl , NCBI gene |
Variants
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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 | Inferred EVA rsID | Year Published | PubMed ID(s) | Acknowledgements |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 986 | Great Dane Rottweiler | Leukoencephalomyelopathy | NAPEPLD | insertion, small (<=20) | Naturally occurring variant | CanFam3.1 | 18 | g.16987327_16987328insC | c.345_346insC | p.(E116Rfs*186) | 2018 | 29643404 | |||||
| 985 | Leonberger | Leukoencephalomyelopathy | NAPEPLD | missense | Naturally occurring variant | CanFam3.1 | 18 | g.16987520G>C | c.538G>C | p.(A180P) | 2018 | 29643404 |
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.
| 2018 | Minor, K.M., Letko, A., Becker, D., Drögemüller, M., Mandigers, P.J.J., Bellekom, S.R., Leegwater, P.A.J., Stassen, Q.E.M., Putschbach, K., Fischer, A., Flegel, T., Matiasek, K., Ekenstedt, K.J., Furrow, E., Patterson, E.E., Platt, S.R., Kelly, P.A., Cassidy, J.P., Shelton, G.D., Lucot, K., Bannasch, D.L., Martineau, H., Muir, C.F., Priestnall, S.L., Henke, D., Oevermann, A., Jagannathan, V., Mickelson, J.R., Drögemüller, C. : |
| Canine NAPEPLD-associated models of human myelin disorders. Sci Rep 8:5818, 2018. Pubmed reference: 29643404 . DOI: 10.1038/s41598-018-23938-7. | |
| 2013 | Eagleson, J.S., Kent, M., Platt, S.R., Rech, R.R., Howerth, E.W. : |
| MRI findings in a rottweiler with leukoencephalomyelopathy. J Am Anim Hosp Assoc 49:255-61, 2013. Pubmed reference: 23690496 . DOI: 10.5326/JAAHA-MS-5864. | |
| Hirschvogel, K., Matiasek, K., Flatz, K., Drögemüller, M., Drögemüller, C., Reiner, B., Fischer, A. : | |
| Magnetic resonance imaging and genetic investigation of a case of rottweiler leukoencephalomyelopathy. BMC Vet Res 9:57, 2013. Pubmed reference: 23531239 . DOI: 10.1186/1746-6148-9-57. | |
| 2008 | Oevermann, A., Bley, T., Konar, M., Lang, J., Vandevelde, M. : |
| A novel leukoencephalomyelopathy of Leonberger dogs. J Vet Intern Med 22:467-71, 2008. Pubmed reference: 18371035 . DOI: 10.1111/j.1939-1676.2008.0068.x. | |
| 2003 | Davies, D.R., Irwin, P.J. : |
| Degenerative neurological and neuromuscular disease in young rottweilers. J Small Anim Pract 44:388-94, 2003. Pubmed reference: 14510327 . | |
| 1993 | Mandigers, P.J.J., Vannes, J.J., Knol, B.W., Ubbink, G.J., Gruys, E. : |
| Hereditary Necrotising Myelopathy in Kooiker Dogs Research in Veterinary Science 54:118-123, 1993. Pubmed reference: 8434139 . | |
| 1992 | Baum, F., de Lahunta, A., Trotter, E.J. : |
| Cervical fibrotic stenosis in a young Rottweiler. J Am Vet Med Assoc 201:1222-4, 1992. Pubmed reference: 1429164 . | |
| Chrisman, C.L. : | |
| Neurological diseases of rottweilers: neuroaxonal dystrophy and leukoencephalomalacia Journal of Small Animal Practice 33:500-504, 1992. DOI: 10.1111/j.1748-5827.1992.tb01033.x. | |
| 1989 | Slocombe, R.F., Mitten, R., Mason, T.A. : |
| Leucoencephalomyelopathy in Australian Rottweiler dogs. Aust Vet J 66:147-50, 1989. Pubmed reference: 2735894 . | |
| 1987 | Lewis, D.G., Newsholme, S.J. : |
| Pseudo cervical spondylopathy in the rottweiler (letter) Journal of Small Animal Practice 28:1178 only, 1987. DOI: 10.1111/j.1748-5827.1987.tb01342.x. | |
| 1986 | Wouda, W., van Nes, J.J. : |
| Progressive ataxia due to central demyelination in Rottweiler dogs. Vet Q 8:89-97, 1986. Pubmed reference: 3727341 . DOI: 10.1080/01652176.1986.9694028. | |
| 1984 | Gamble, D.A., Chrisman, C.L. : |
| A leukoencephalomyelopathy of rottweiler dogs. Vet Pathol 21:274-80, 1984. Pubmed reference: 6730216 . | |
| 1977 | Averill, D.R., Bronson, R.T. : |
| Inherited necrotizing myelopathy of Afghan Hounds Journal of Neuropathology and Experimental Neurology 36:734-737, 1977. Pubmed reference: 886368 . |
Edit History
- Created by Frank Nicholas on 23 Apr 2013
- Changed by Frank Nicholas on 18 Apr 2018