Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 254210 (trait) , 118490 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0009689: congenital myasthenic syndrome 6

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: 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).
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: