OMIA 002072-9615 : Myasthenic syndrome, congenital, CHAT-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 254210

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: unknown

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.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
CHAT choline O-acetyltransferase Canis lupus familiaris 28 NC_006610.3 (1480364..1528858) 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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Old Danish Pointing Dog Myasthenic syndrome, congenital CHAT missense 28 g.1484906G>A c.??G>A p.V29M 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.
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