OMIA 001514-9615 : Acral mutilation syndrome in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 223900 , 201300 , 608654 , 613115 , 614213

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2016

Species-specific name: hereditary sensory neuropathy

Species-specific symbol: AMS

Mapping: Plassais et al. (2016) "highlighted a common homozygous haplotype of 1.8 Mb (chr4:70,6–72,4Mb) shared by all affected dogs in the four sporting breeds (listed in this entry)"

Molecular basis: "Targeted high-throughput sequencing of [the positional candidate segment] in 4 affected and 4 unaffected dogs" enabled Plassais et al. (2016) to identify 478 variants, only one of which "perfectly segregated with the expected recessive inheritance in 300 sporting dogs of known clinical status, while it was never present in 900 unaffected dogs from 130 other breeds. This variant, located 90 kb upstream of the GDNF gene, a highly relevant neurotrophic factor candidate gene, lies in [the last exon of] a long intergenic non-coding RNAs (lincRNA), GDNF-AS." The authors also reported that " Functional analyses (qRT-PCR, EMSA) confirmed that the mutation alters the binding of regulatory complex, leading to a significant decrease of both GDNF and GDNF-AS mRNA expression levels."

Clinical features: As summarised by Plassais et al. (2016): " Clinical signs appear in young puppies and consist of acral analgesia, with or without sudden intense licking, biting and severe self-mutilation of the feet, whereas proprioception, motor abilities and spinal reflexes remain intact"

Breeds: English Pointer, English Springer Spaniel, French Spaniel, German Shorthair Pointer.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
GDNF glial cell derived neurotrophic factor Canis lupus familiaris 4 NC_006586.3 (70966694..70991860) GDNF Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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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
Acral mutilation syndrome GDNF regulatory "This variant, located 90 kb upstream of the GDNF gene, a highly relevant neurotrophic factor candidate gene, lies in [the last exon of] a long intergenic non-coding RNAs (lincRNA), GDNF-AS." 2016 28033318

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.
2016 Plassais , J., Lagoutte, L., Correard, S., Paradis, M., Guaguère, E., Hédan, B., Pommier, A., Botherel, N., Cadiergues, M.-C., Pilorge, P., Silversides, D., Bizot, M., Samuels, M., Arnan, C., Johnson, R., Hitte, C., Salbert, G., Méreau, A., Quignon, P., Derrien, T., André, C. :
A Point Mutation in a lincRNA Upstream of GDNF Is Associated to a Canine Insensitivity to Pain: A Spontaneous Model for Human Sensory Neuropathies PLoS Genetics 12: e1006482, 2016. Pubmed reference: 28033318. DOI: 10.1371/journal.pgen.1006482.
2010 Bardagí, M., Montoliu, P., Ferrer, L., Fondevila, D., Pumarola, M. :
Acral mutilation syndrome in a miniature pinscher. J Comp Pathol 144:235-8, 2010. Pubmed reference: 20961556. DOI: 10.1016/j.jcpa.2010.08.014.
2005 Paradis, M., de Jaham, C., Page, N., Sauve, F., Helie, P. :
Acral mutilation and analgesia in 13 French spaniels. Vet Dermatol 16:87-93, 2005. Pubmed reference: 15842538. DOI: 10.1111/j.1365-3164.2005.00443.x.
1984 Cummings, J.F. , de Lahunta, A., Simpson, S.T., McDonald, J.M. :
Reduced substance P-like immunoreactivity in hereditary sensory neuropathy of pointer dogs. Acta Neuropathol. 63:33-40, 1984. Pubmed reference: 6203326.
1983 Cummings, JF., de Lahunta, A., Braund, KG., Mitchell, WJ. :
Hereditary sensory neuropathy. Nociceptive loss and acral mutilation in pointer dogs: canine hereditary sensory neuropathy. Am J Pathol 112:136-8, 1983. Pubmed reference: 6574711.
1981 Cummings, JF., de Lahunta, A., Winn, SS. :
Acral mutilation and nociceptive loss in English pointer dogs. A canine sensory neuropathy. Acta Neuropathol 53:119-27, 1981. Pubmed reference: 6259871.
1973 Pivník, L. :
[Comparative problems of acrodystrophic neuropathies in man and dogs]. Schweiz Arch Neurol Neurochir Psychiatr. 112:365–371, 1973. Pubmed reference: 4725277.
1964 Sanda, A., Pivník, L. :
Die zehernekrose bei kurghaarigen. Vorstehlunden Kleintierproxis 9:76 only, 1964.

Edit History


  • Created by Frank Nicholas on 28 Feb 2011
  • Changed by Frank Nicholas on 31 Dec 2016