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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

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
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.
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Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2020). OMIA:002072-9615: 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.

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


  • Created by Frank Nicholas on 09 Nov 2016
  • Changed by Frank Nicholas on 09 Nov 2016
  • Changed by Frank Nicholas on 15 May 2020