OMIA:002072-9615 : Myasthenic syndrome, congenital, CHAT-related in Canis lupus familiaris |
Categories: Nervous system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 254210 (trait) , 118490 (gene)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2007
Species-specific name: Congenital myasthenic syndrome
Species-specific symbol: CMS
Species-specific description: Congenital myasthenic syndrome is a neuromuscular disorder of Old Danish Pointing Dogs characterized by transient paralysis after exercise. The causative mutation in ChAT causes reduced presynaptic acetylcholine synthesis. A genetic test is available.
Edited by Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT
History: Congenital myasthenic syndrome was first recognized in Old Danish Pointing Dogs in 1977 (Flagstad, 1982).
Mapping: CFA28
Molecular basis: The causative mutation is a G to A substitution in exon 6 of the Choline O-acetyltransferase gene (ChAT). This changes an amino acid codon from valine to methionine (Proschowsky et al., 2007).
Clinical features: Affected dogs can run normally for 5 to 30 minutes, but then begin to take shorter and shorter strides. Eventually, they fall down with flexed legs. The signs disappear after several minutes of rest, but will recur if exercise is continued. These dogs have no detectable antibodies against acetylcholine receptors, and have normal numbers of acetylcholine receptors at the neuromuscular junction. In contrast to dogs with myasthenia gravis, neither edrophonium nor neostigmine has any effect on the clinical signs (Proschowsky et al., 2007).
Pathology: The clinical signs are caused by a presynaptic defect that reduces synthesis of acetylcholine in affected dogs (Proschowsky et al., 2007).
Prevalence: Reported cases have been limited to Denmark.
Control: The population of Old Danish Pointing Dogs in Denmark is small, and importation of for breeding purposes is not allowed. All dogs should be tested prior to breeding. To avoid production of affected dogs, but allow for population expansion and gradual eradication of the mutation, carrier dogs may be bred with homozygous normal dogs (Proschowsky et al., 2007).
Genetic testing: A test is available to Danish breeders of Old Danish Pointing Dogs (Proschowsky et al., 2007).
Breed: Old Danish Pointing Dog (Dog) (VBO_0000668).
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| CHAT | choline O-acetyltransferase | Canis lupus familiaris | 28 | NC_051832.1 (1656110..1708901) | CHAT | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 61 | Old Danish Pointing Dog (Dog) | Myasthenic syndrome, congenital | CHAT | missense | Naturally occurring variant | CanFam3.1 | 28 | g.1484906G>A | c.85G>A | p.(V29M) | XM_005637485.3; XP_005637542.1 | 2007 | 17586598 | 20181218 Thanks to Maarten de Groot for advising FN of the genomic location of this variant. |
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.
| 2023 | Pugliese, A., Holland, S.H., Rodolico, C., Lochmüller, H., Spendiff, S. : |
| Presynaptic congenital myasthenic syndromes: understanding clinical phenotypes through in vivo models. J Neuromuscul Dis :, 2023. Pubmed reference: 37212067 . DOI: 10.3233/JND-221646. | |
| 2020 | Mignan, T., Targett, M., Lowrie, M. : |
| Classification of myasthenia gravis and congenital myasthenic syndromes in dogs and cats. J Vet Intern Med 34:1707-1717, 2020. Pubmed reference: 32668077 . DOI: 10.1111/jvim.15855. | |
| 2007 | Proschowsky, HF., Flagstad, A., Cirera, S., Joergensen, CB., Fredholm, M. : |
| Identification of a mutation in the CHAT gene of Old Danish Pointing Dogs affected with congenital myasthenic syndrome. J Hered 98:539-43, 2007. Pubmed reference: 17586598 . DOI: 10.1093/jhered/esm026. | |
| 1993 | Flagstad, A. : |
| Development of the Electrophysiological Pattern in Congenital Myasthenic Syndrome Progress in Veterinary Neurology 4:126-134, 1993. | |
| 1982 | Flagstad, A. : |
| A new hereditary neuromuscular disease in the dog breed "Gammel Dansk Honsehund". Genetic investigations. Hereditas 96:211-4, 1982. Pubmed reference: 7201985 . |
Edit History
- Changed by Frank Nicholas on 09 Nov 2016
- Created by Frank Nicholas on 09 Nov 2016
- Changed by Frank Nicholas on 15 May 2020