OMIA:001788-9615 : Leukoencephalomyelopathy, NAPEPLD-related in Canis lupus familiaris (dog)

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 612334 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2018

Cross-species summary: Renamed to Leukoencephalomyelopathy, NAPEPLD-related [09/06/2023] to reflect that information focuses on leukoencephalomyelopathy due to variants in the NAPEPLD gene. See other entries for other forms of myelin disease; e.g. various entries relating to 'Leukodystrophy' in OMIA

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: Great Dane (Dog) (VBO_0200623), Leonberger (Dog) (VBO_0200819), Rottweiler (Dog) (VBO_0201143).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

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


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 Year Published PubMed ID(s) Acknowledgements
986 Great Dane (Dog) Rottweiler (Dog) Leukoencephalomyelopathy NAPEPLD insertion, small (<=20) Naturally occurring variant CanFam3.1 18 g.16987327_16987328insC c.345_346insC p.(E116Rfs*186) 2018 29643404
985 Leonberger (Dog) Leukoencephalomyelopathy NAPEPLD missense Naturally occurring variant CanFam3.1 18 g.16987520G>C c.538G>C p.(A180P) 2018 29643404

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:001788-9615: 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.

2023 Meadows, J.R.S., Kidd, J.M., Wang, G.D., Parker, H.G., Schall, P.Z., Bianchi, M., Christmas, M.J., Bougiouri, K., Buckley, R.M., Hitte, C., Nguyen, A.K., Wang, C., Jagannathan, V., Niskanen, J.E., Frantz, L.A.F., Arumilli, M., Hundi, S., Lindblad-Toh, K., Ginja, C., Agustina, K.K., André, C., Boyko, A.R., Davis, B.W., Drögemüller, M., Feng, X.Y., Gkagkavouzis, K., Iliopoulos, G., Harris, A.C., Hytönen, M.K., Kalthoff, D.C., Liu, Y.H., Lymberakis, P., Poulakakis, N., Pires, A.E., Racimo, F., Ramos-Almodovar, F., Savolainen, P., Venetsani, S., Tammen, I., Triantafyllidis, A., vonHoldt, B., Wayne, R.K., Larson, G., Nicholas, F.W., Lohi, H., Leeb, T., Zhang, Y.P., Ostrander, E.A. :
Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture. Genome Biol 24:187, 2023. Pubmed reference: 37582787. DOI: 10.1186/s13059-023-03023-7.
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.
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.

Edit History

  • Created by Frank Nicholas on 23 Apr 2013
  • Changed by Frank Nicholas on 18 Apr 2018
  • Changed by Imke Tammen2 on 09 Jun 2023