OMIA:000685-9615 : Myasthenic syndrome, congenital, CHRNE-related in Canis lupus familiaris (dog)

In other species: taurine cattle , indicine cattle (zebu)

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 605809 (trait) , 616324 (trait) , 608931 (trait) , 100725 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2015

Species-specific name: Jack Russel terrier type congenital myasthenic syndrome; post-synaptic congenital myasthenic syndrome; myasthenia gravis-like disease

Molecular basis: By sequencing two positional functional candidate genes, Rinz et al. (2015) concluded that a likely causal mutation in Jack Russell Terriers is "a single base insertion [c.633_634insC] in exon 7 of CHRNE that predicts a frameshift mutation and a premature stop codon [p.Gly212Argfs*274]". Herder et al. (2017) investigated a litter of Heideterriers (a "nascent" breed not recognized by the FCI), in which 4 out of 11 puppies showed pronounced muscle weakness. Only one of these puppies was available for genetic analysis. Herder et al. (2017) performed whole genome sequencing and identified a homozygous single nucleotide insertion into the coding sequence of the CHRNE gene (XM_014113502.1:c.1436_1437insG). The insertion was predicted to lead to a frameshift and premature stop codon (XP_013968977.1:p.Ser479ArgfsTer14). This variant was absent from the genomes of 274 control dogs. Based on the earlier findings in Jack Russell Terriers and other species, Herder et al. (2017) concluded that "it is plausible that the CHRNE variant may have caused a myasthenia gravis-like disease in the investigated puppy."

Clinical features: Rinz et al. (2015) reported that affected Jack Russell Terrier (JRT) pups appeared normal until 6 weeks of age. "Affected JRT pups showed generalized muscle weakness at 7 weeks of age, walking only briefly for 10–15 short-strided steps before sitting or lying down." Treatment with anticholinesterase drug resulted in temporary improvement of muscle weakness. "Development of drug resistance necessitated euthanasia." Herder et al. (2017): "In a litter of Heideterriers, four out of 11 puppies showed a lack of reflexes and coordination of the front limbs 6 days after birth. Consciousness and general condition of these animals was reported to be normal, and none showed fever. The four affected puppies displayed weakness progressing over the course of the day and peaking at night time. The most severely affected animal showed falling to the side and recumbency, while still being alert and trying to play in this position."

Pathology: Rinz et al. (2015): "No indication of a primary nervous system or muscle disorder was found on post-mortem examination [of affected Jack Russell Terriers]. Occasional groups of atrophic myofibers of both fiber types were noted in cryosections stained with the myofibrillar ATPase reaction. Several end-plates were identified by the esterase reaction product staining, but no AChRs were detectable in serial cryosections by labeling with fluorescent α-bungarotoxin." Herder et al. (2017) reported lack of significant pathological findings in most muscles except for mild lipomatosis musculorum in the M. triceps in a Heideterrier.

Breeds: Heideterrier (Dog) (VBO_0200666), Jack Russell Terrier (Dog) (VBO_0200724).
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:

Symbol Description Species Chr Location OMIA gene details page Other Links
CHRNE cholinergic receptor, nicotinic, epsilon (muscle) Canis lupus familiaris 5 NC_051809.1 (31801741..31815685) CHRNE 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 Year Published PubMed ID(s) Acknowledgements
614 Jack Russell Terrier (Dog) Myasthenic syndrome, congenital, due to CHRNE CHRNE insertion, small (<=20) Naturally occurring variant CanFam3.1 5 g.31705136_31705137insC c.636_637insC p.(G212Rfs*274) ENSCAFT00000083466.1; ENSCAFP00000057633.1; published as c.633_634insC, coordinates in the table updated in accordance to HGVS 3'-rule 2015 26429099
804 Heideterrier (Dog) Myasthenic syndrome, congenital, due to CHRNE CHRNE insertion, small (<=20) Naturally occurring variant CanFam3.1 5 g.31707450_31707451insG c.1436_1437insG p.(S479Rfs*14) XM_014113502.1; XP_013968977.1 2017 28508416

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:000685-9615: 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.

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.
2017 Herder, V., Ciurkiewicz, M., Baumgärtner, W., Jagannathan, V., Leeb, T. :
Frame-shift variant in the CHRNE gene in a juvenile dog with suspected myasthenia gravis-like disease. Anim Genet 48:625, 2017. Pubmed reference: 28508416. DOI: 10.1111/age.12558.
2015 Rinz, C.J., Lennon, V.A., James, F., Thoreson, J.B., Tsai, K.L., Starr-Moss, A.N., Humphries, H.D., Guo, L.T., Palmer, A.C., Clark, L.A., Shelton, G.D. :
A CHRNE frameshift mutation causes congenital myasthenic syndrome in young Jack Russell Terriers. Neuromuscul Disord 25:921-7, 2015. Pubmed reference: 26429099. DOI: 10.1016/j.nmd.2015.09.005.
1984 Oda, K., Lambert, E.H., Lennon, V.A., Palmer, A.C. :
Congenital canine myasthenia gravis: I. Deficient junctional acetylcholine receptors. Muscle Nerve 7:705-16, 1984. Pubmed reference: 6543919. DOI: 10.1002/mus.880070904.
Oda, K., Lennon, V.A., Lambert, E.H., Palmer, A.C. :
Congenital canine myasthenia gravis: II. Acetylcholine receptor metabolism. Muscle Nerve 7:717-24, 1984. Pubmed reference: 6543920. DOI: 10.1002/mus.880070905.
Wallace, M.E., Palmer, A.C. :
Recessive mode of inheritance in myasthenia gravis in the Jack Russell terrier. Vet Rec 114:350, 1984. Pubmed reference: 6719791.
1978 Palmer, A.C., Goodyear, J.V. :
Congenital myasthenia in the Jack Russel Terrier (correspondence) Veterinary Record 103:433-434, 1978. Pubmed reference: 741601.
1974 Palmer, A.C., Barker, J. :
Myasthenia in the dog. Vet Rec 95:452-4, 1974. Pubmed reference: 4446286.

Edit History


  • Created by Frank Nicholas on 09 Nov 2016
  • Changed by Frank Nicholas on 09 Nov 2016
  • Changed by Tosso Leeb on 16 Jun 2017
  • Changed by Imke Tammen2 on 02 May 2023