Possibly relevant human trait(s) and/or gene(s) (MIM number): 616505

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: unknown

Key variant known: yes

Year key variant first reported: 2017

Mapping: Duchesne et al. (2017): "Genotyping of 12 affected calves followed by homozygosity mapping identified a single 3.1 Mb homozygous interval at the telomeric end of bovine chromosome 7".

Molecular basis: Duchesne et al. (2017) identified SNPs in the mapped candidate region by comparison of whole-genome sequence of two homozygous affecteds, one heterozygote and one homozygote normal. Filtering of those SNPs by consistency with presumed genotype based on pedigree, with occurrence only within this breed, and by severity of presumed function enabled Duchesne et al. (2017) to identifiy a "C/T SLC25A46 substitution [c.376C>T that] leads to replacement of an arginine by a cysteine [p.Arg126Cys], in the first transmembrane helix of the protein" as a likely causal variant.

Clinical features: Duchesne et al. (2017): "In the late 2000’s, such an outbreak was described in the French Rouge-des-Prés breed with a new sensorimotor polyneuropathy named “Syndrome des veaux tourneurs” (“Turning calves syndrome”) because of a propensity of the affected calves to turn around themselves before falling down [Timsit et al., 2011]. This neurodegenerative disease is characterized by an early onset of ataxia, especially of hindlimbs, and paraparesia affecting young calves (2–6 weeks old). Despite symptomatic care, nervous symptoms progress over the next months, leading to repetitive falls and ultimately resulting in permanent recumbency and inevitably euthanasia. Degenerative lesions involve both the general proprioceptive sensory and upper motor neuron motor systems [Timsit et al., 2011]."

Also, Duchesne et al. (2017) "created a mouse knock-out model and determined that disruption of this gene dramatically disturbed mitochondrial dynamics in various organs that resulted in altered metabolism and early death, indirectly confirming the gene identification in cattle."

Breed: Rouge-des-Prés.

Associated gene: