Categories: Nervous system phene

Possibly relevant human trait(s) and/or gene(s) (MIM number): 603788 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2021

Species-specific description: Jacinto et al. (2021) "characterize the clinicopathologic features of a Belgian Blue x Holstein crossbred calf with paradoxical myotonia congenita, craniofacial dysmorphism, and myelodysplasia, and ... identify the most likely genetic etiology."

Inheritance: Jacinto et al. (2021) "speculate that the mutation occurred either as a parental germline mutation or post-zygotically in the developing embryo."

Molecular basis: Jacinto et al. (2021): "Whole-genome sequencing revealed a heterozygous missense variant in KCNG1 affecting an evolutionary conserved residue (p.Trp416Cys). The mutation was predicted to be deleterious and to alter the pore helix of the ion transport domain of the transmembrane protein. The identified variant was present only in the affected calf and not seen in more than 5200 other sequenced bovine genomes. ... This study implicates an important role for KCNG1 as a member of the potassium voltage-gated channel group in neurodegeneration."

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

Clinical features: Jacinto et al. (2021): "The calf displayed episodes of exercise-induced generalized myotonic muscle stiffness accompanied by increase in serum potassium. It also showed slight flattening of the splanchnocranium with deviation to the right side."

Pathology: Jacinto et al. (2021): "On gross pathology, myelodysplasia (hydrosyringomielia and segmental hypoplasia) in the lumbosacral intumescence region was noticed. Histopathology of the muscle profile revealed loss of the main shape in 5.3% of muscle fibers."

Associated gene: