Categories: Muscle phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 601003 (trait) , 108730 (gene)

Links to MONDO diseases:

• MONDO:0010977: Brody myopathy

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: CMD1

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 2.12 Mb region on BTA25 in which 12 affected calves were significantly more homozygous for the same allele at each of many SNPs, when compared with 14 normal controls. An investigation of comparative candidate genes in this region identified six possible candidate genes. Sequencing revealed the causative molecular lesion in the ATPA2A1 gene, whose peptide is involved in calcium flow into the sarcoplasmic reticulum.

Molecular basis: "A missense mutation (C1676T) leading to a R559C substitution in exon 14 of ATP2A1" (Charlier et al., 2008)

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

Clinical features: "Calves affected by CMD1 show impaired swallowing, fatigue upon stimulation or exercise, and muscle myotonia resulting in an inability to flex limbs and injurious falling. CMD1 calves usually die within a few weeks as a result of respiratory complications." (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: