OMIA 002279-9615 : Ataxia, spinocerebellar, SLC12A6-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 218000

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2019

Molecular basis: Van Poucke et al. (2019): "whole-exome sequencing identified the SLC12A6 NC_006612.3(XM_014109414.2): c.178_181delinsCATCTCACTCAT (p.(Met60Hisfs*14)) truncating variant. This loss-of-function variant perfectly segregated within the affected Malinois family in an autosomal recessive way and was not found in 562 additional reference dogs from 18 different breeds, including Malinois."

Clinical features: Van Poucke et al. (2019): "progressive spinocerebellar ataxia, which is the most important feature of the canine phenotype, hindlimb paresis, and myokymia-like muscle contractions"

Breed: Malinois.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
SLC12A6 solute carrier family 12 (potassium/chloride transporter), member 6 Canis lupus familiaris 30 NC_051834.1 (868821..957072) SLC12A6 Homologene, Ensembl, NCBI gene

Variants

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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.

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
Malinois Ataxia, spinocerebellar, SLC12A6-related SLC12A6 delins, small (<=20) CanFam3.1 30 c.178_181delinsCATCTCACTCAT p.(Met60Hisfs*14) "The INDEL involves a 12-bp insertion (CATCTCACTCAT) and a 4-bp deletion (ATGA), most probably generated by a template-switch process with an inverted repeat and an inverted spacer (Fig. 2). The variant is located in exon 1a and causes a frameshift at codon 60, leading to a premature stopcodon 14 codons downstream in all transcripts containing exon 1a (Fig. 2). The SLC12A6 NC_006612.3(XM_014109414.2): c.178_181delinsCATCTCACTCAT (p.(Met60Hisfs*14)) variant was deposited in the EVA database (URL: https://www.ebi.ac.uk/eva/; Project: PRJEB30850; Analyses: ERZ802317)" (Van Poucke et al., 2019) 2019 31160700

Reference


2019 Van Poucke, M., Stee, K., Sonck, L., Stock, E., Bosseler, L., Van Dorpe, J., Van Nieuwerburgh, F., Deforce, D., Peelman, L.J., Van Ham, L., Bhatti, S.F.M., Broeckx, B.J.G. :
Truncating SLC12A6 variants cause different clinical phenotypes in humans and dogs. Eur J Hum Genet 27:1561-1568, 2019. Pubmed reference: 31160700. DOI: 10.1038/s41431-019-0432-3.

Edit History


  • Created by Frank Nicholas on 18 Jun 2020
  • Changed by Frank Nicholas on 18 Jun 2020