OMIA:000770-9615 : Tremor, X-linked in Canis lupus familiaris (dog) |
In other species: pig , rabbit
Categories: Nervous system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 312080 (trait) , 300401 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: X-linked recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 1990
Species-specific name: Shaking pup
Species-specific symbol: SHP
Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous disorder in humans, mice and rats), Nadon et al. (1990) reported the causative mutation as "a point mutation at position 219 of the coding sequence [of the PLP gene; now called PLP1] that results in a histidine to proline change in the protein". According to the current variant nomenclature as of 2013 this corresponds to a c.110A>C or p.H37P missense variant.
Genetic engineering:
Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: Affected dogs may be smaller than littermates, and often present with difficulty standing, ataxia, and generalised tremors that typically appear at 10-12 days of age (Griffiths et al., 1981). Death often occurs at 3-4 months of age (Griffiths et al., 1981; Nadon et al., 1990). IT thanks DVM student Judith Browne, who provided the basis of this contribution in May 2023.
Pathology: This disease is characterised by hypomyelination and reduced numbers of mature oligodendrocytes in the central nervous system (CNS) only, with abnormalities most pronounced in the cerebrum and optic nerve (Griffiths et al., 1981; Duncan et al., 1983). Histological features include shortened internodes, reduced thickness or absence of myelin sheaths of CNS axons, and expansion of the perinuclear sheaths and rough endoplasmic reticulum (RER) of oligodendrocytes (Griffiths et al., 1981; Duncan et al.,1983). Due to the X-linked mode of inheritance this disease affects males predominately. Due to X-inactivation in females, animals that are heterozygotes can present with tremors that disappear over time, and can present with myelin mosaicism in the CNS (Duncan et al., 1987). IT thanks DVM student Judith Browne, who provided the basis of this contribution in May 2023.
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| PLP1 | proteolipid protein 1 | Canis lupus familiaris | X | NC_051843.1 (78808649..78825317) | PLP1 | 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.
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 82 | Springer Spaniel (Dog) | Tremor, X-linked | PLP1 | missense | Naturally occurring variant | CanFam3.1 | X | g.77200833A>C | c.110A>C | p.(H37P) | 1990 | 1723945 | Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:000770-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70
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.
| 2004 | Yamaya, Y., Iwakami, E., Goto, M., Koie, H., Watari, T., Tanaka, S., Takeuchi, A., Tokuriki, M. : |
| A case of shaker dog disease in a miniature dachshund. J Vet Med Sci 66:1159-60, 2004. Pubmed reference: 15472486. | |
| 1998 | Cuddon, P.A., Lipsitz, D., Duncan, I.D. : |
| Myelin mosaicism and brain plasticity in heterozygous females of a canine X-linked trait Annals of Neurology 44:771-779, 1998. Pubmed reference: 9818933. DOI: 10.1002/ana.410440511. | |
| 1997 | Tosic, M., Matthey, B., Gow, A., Lazzarini, R.A., Matthieu, J.M. : |
| Intracellular transport of the DM-20 bearing shaking pup (shp) mutation and its possible phenotypic consequences. J Neurosci Res 50:844-52, 1997. Pubmed reference: 9418971. | |
| 1996 | Nadon, N.L., Duncan, I.D. : |
| Molecular analysis of glial cell development in the canine shaking pup mutant Developmental Neuroscience 18:174-184, 1996. Pubmed reference: 8894446. | |
| 1995 | Vanvooren, N. : |
| A suspected case of idiopathic generalised tremor (shaker disease) in a shih tzu Veterinary Record 136:568, 1995. Pubmed reference: 7676584. | |
| 1990 | Nadon, N.L., Duncan, I.D., Hudson, L.D. : |
| A point mutation in the proteolipid protein gene of the shaking pup interrupts oligodendrocyte development. Development 110:529-537, 1990. Pubmed reference: 1723945. | |
| 1987 | Duncan, I.D., Hammang, J.P., Jackson, K.F. : |
| Myelin mosaicism in female heterozygotes of the canine shaking pup and myelin-deficient rat mutants. Brain Res 402:168-72, 1987. Pubmed reference: 3828784. | |
| Yanagisawa, K., Moller, J.R., Duncan, I.D., Quarles, R.H. : | |
| Disproportional expression of proteolipid protein and DM-20 in the X-linked, dysmyelinating shaking pup mutant. J Neurochem 49:1912-7, 1987. Pubmed reference: 2445922. | |
| 1986 | Inuzuka, T., Duncan, I.D., Quarles, R.H. : |
| Myelin proteins in the CNS of 'shaking pups'. Brain Res 392:43-50, 1986. Pubmed reference: 3708384. | |
| 1983 | Bray, G.M., Duncan, I.D., Griffiths, I.R. : |
| 'Shaking pups': a disorder of central myelination in the spaniel dog. IV. Freeze-fracture electron microscopic studies of axons, oligodendrocytes and astrocytes in the spinal cord white matter. Neuropathol Appl Neurobiol 9:369-78, 1983. Pubmed reference: 6646344. | |
| Duncan, I.D., Griffiths, I.R., Munz, M. : | |
| 'Shaking pups': a disorder of central myelination in the spaniel dog. III. Quantitative aspects of glia and myelin in the spinal cord and optic nerve. Neuropathol Appl Neurobiol 9:355-68, 1983. Pubmed reference: 6646343. | |
| 1981 | Griffiths, I.R., Duncan, I.D., McCulloch, M. : |
| Shaking pups: a disorder of central myelination in the spaniel dog. II. Ultrastructural observations on the white matter of the cervical spinal cord. J Neurocytol 10:847-58, 1981. Pubmed reference: 7310479. | |
| Griffiths, I.R., Duncan, I.D., McCulloch, M., Harvey, M.J. : | |
| Shaking pups: a disorder of central myelination in the Spaniel dog. Part 1. Clinical, genetic and light-microscopical observations. J Neurol Sci 50:423-33, 1981. Pubmed reference: 7196438. |
Edit History
- Created by Frank Nicholas on 12 Sep 2005
- Changed by Frank Nicholas on 14 Sep 2011
- Changed by Frank Nicholas on 12 Dec 2011
- Changed by Frank Nicholas on 19 Sep 2012
- Changed by Tosso Leeb on 29 May 2013
- Changed by Imke Tammen2 on 18 May 2023