OMIA:002740-9615 : Polyneuropathy, hypomyelinating, SH3TC2-related in Canis lupus familiaris (dog)
Categories: Nervous system phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Probably autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2023
Cross-species summary: Congenital polyneuropathy due to underproduction of myelin, which is exclusively affecting the peripheral nervous system. Similar to Charcot-Marie-Tooth disease in humans.
Species-specific name: congenital hypomyelinating polyneuropathy; HPN
Species-specific description: Cook et al. (2023): “Congenital hypomyelinating polyneuropathy (HPN) restricted to the peripheral nervous system was reported in 1989 in two Golden Retriever (GR) littermates [see OMIA:001292-9615 : Polyneuropathy, generic in Canis lupus familiaris]. Recently, four additional cases of congenital HPN in young, unrelated GRs were diagnosed via neurological examination, electrodiagnostic evaluation, and peripheral nerve pathology.”
Molecular basis: Cook et al. (2023): “Whole-genome sequencing was performed on all four [affected Golden Retriever] …, and variants from each dog were compared to variants found across >1,000 other dogs, all presumably unaffected with HPN. Likely causative variants were identified for each HPN-affected GR.” The authors identified 3 likely causal variants in functional candidate genes MTMR2, MPZ and SH3TC2. “Case 4 possessed a homozygous SH3TC2 (SH3 domain and tetratricopeptide repeats 2) variant in exon 11 of 17 … . This C to T nonsense mutation (CFA4: 60,798,310 (XP_038391009.1:p.Arg642*)) was private to Case 4 compared to 1,026 other dogs with WGS data available … .” Please see the gene specific OMIA entries for details about the other variants.
Have human generated variants been created, e.g. through genetic engineering and gene editing
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|SH3TC2||SH3 domain and tetratricopeptide repeats 2||Canis lupus familiaris||4||NC_051808.1 (60283914..60388188)||SH3TC2||Homologene, Ensembl , NCBI gene|
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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.
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||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1593||Golden Retriever||Polyneuropathy, hypomyelinating, SH||SH3TC2||nonsense (stop-gain)||Naturally occurring variant||UU_Cfam_GSD_1.0||4||g.60798310C>T||c.1924C>T||p.(R642*)||XM_038535081.1; XP_038391009.1; reported in one affected dog with coordinates relating to a different transcript as XM_038568229.1:c.1479G>A||2023||37400349|
Cite this entry
|2023||Cook, S., Hooser, B.N., Williams, D.C., Kortz, G., Aleman, M., Minor, K., Koziol, J., Friedenberg, S.G., Cullen, J.N., Shelton, G.D., Ekenstedt, K.J. :|
|Canine models of Charcot-Marie-Tooth: MTMR2, MPZ, and SH3TC2 variants in golden retrievers with congenital hypomyelinating polyneuropathy. Neuromuscul Disord , 2023. Pubmed reference: 37400349. DOI: 10.1016/j.nmd.2023.06.007.|
- Created by Imke Tammen2 on 22 Jul 2023