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

In other species: cattle

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 605809 , 616324 , 608931

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2015

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."

Breeds: Heideterrier, Jack Russell Terrier.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
CHRNE cholinergic receptor, nicotinic, epsilon (muscle) Canis lupus familiaris 5 NC_006587.3 (31696710..31707639) CHRNE Homologene, Ensembl, NCBI gene

Variants

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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
Jack Russell Terrier Myasthenic syndrome, congenital, due to CHRNE CHRNE insertion, small (<=20) c.633_634insC p.Gly212Argfs*274 2015 26429099
Heideterrier Myasthenic syndrome, congenital, due to CHRNE CHRNE insertion, small (<=20) CanFam3.1 5 g.31707450_31707451insG c.1436_1437insG p.Ser479ArgfsTer14 2017 28508416

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.
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