Categories: Nervous system phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 604159 (gene) , 614618 (trait)

Links to MONDO diseases: No links.

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 (and was previously called LOC528050 in NCBI). Gill et al. (2012) reported the same mutation in Belgian Blues from the UK.

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

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 (Cattle) (VBO_0000139).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: