OMIA 001451-9913 : Congenital muscular dystonia 2 in Bos taurus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 149400

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2008

Species-specific symbol: CMD2

Species-specific description: In the words of Charlier et al. (2008), "All calves with CMD have episodes of generalized muscle contractures, but careful clinical examination suggested two distinct phenotypes (CMD1 and CMD2."

Mapping: In a pioneering use of tens of thousands of SNP markers ("using either the 25K Affymetrix SNP panel or a custom-made 60K Illumina panel"), Charlier et al. (2008) identified a single 3.61 Mb region on BTA29 in which 7 affected calves were significantly more homozygous for the same allele at each of many SNPs, when compared with 24 normal controls. An investigation of all 13 genes in that region identified the most likely culprit as being SLC6A5, which encodes a glycine transporter.

Molecular basis: "A missense mutation (T809C) in exon 4, resulting in a L270P substitution in the third membrane-spanning domain of GlyT2" (a glycine transporter). (Charlier et al., 2008). The GlyT2 gene is now called SLC6A5 but NCBI Gene calls it LOC528050. Gill et al. (2012) reported the same mutation in Belgian Blues from the UK.

Clinical features: "CMD2 calves suffer severe episodes of myoclonus upon acoustic or tactile stimulation and typically die within a few hours of birth. CMD2 is reminiscent of congenital myoclonus in Hereford cattle" (Charlier et al., 2008)

Breed: Belgian Blue.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
LOC528050 sodium- and chloride-dependent glycine transporter 2 Bos taurus 29 NC_037356.1 (24373268..24316601) LOC528050 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
Belgian Blue Congenital muscular dystonia 2 LOC528050 missense UMD3.1 29 g.24610495T>C c.809T>C p.L270P 2008 18344998 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool; Breed information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (https://www.icbf.com/wp/?page_id=2170)

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.
2012 Gill, J.L., James, V.M., Carta, E., Harris, D., Topf, M., Scholes, S.F., Hateley, G., Harvey, R.J. :
Identification of congenital muscular dystonia 2 associated with an inherited GlyT2 defect in Belgian Blue cattle from the United Kingdom. Anim Genet 43:267-70, 2012. Pubmed reference: 22486497. DOI: 10.1111/j.1365-2052.2011.02255.x.
2008 Charlier, C., Coppieters, W., Rollin, F., Desmecht, D., Agerholm, JS., Cambisano, N., Carta, E., Dardano, S., Dive, M., Fasquelle, C., Frennet, JC., Hanset, R., Hubin, X., Jorgensen, C., Karim, L., Kent, M., Harvey, K., Pearce, BR., Simon, P., Tama, N., Nie, H., Vandeputte, S., Lien, S., Longeri, M., Fredholm, M., Harvey, RJ., Georges, M. :
Highly effective SNP-based association mapping and management of recessive defects in livestock. Nat Genet 40:449-54, 2008. Pubmed reference: 18344998. DOI: 10.1038/ng.96.

Edit History


  • Created by Frank Nicholas on 30 Mar 2008
  • Changed by Frank Nicholas on 07 Oct 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 22 Aug 2012
  • Changed by Frank Nicholas on 21 May 2013
  • Changed by Frank Nicholas on 07 Jun 2013
  • Changed by Frank Nicholas on 16 Aug 2013
  • Changed by Frank Nicholas on 12 Dec 2017