Categories: Nervous system phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 601515 (gene) , 609307 (trait)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal incomplete dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2017

Species-specific name: familial episodic ataxia

Inheritance: Based on the results of mating the two unaffected rams (that had previously produced affected offspring) with unrelated ewes, Mayhew et al. (2012) concluded that this disorder is "a dominant trait, with incomplete penetration of observed clinical signs and variable expressivity."

Molecular basis: Dittmer et al. (2017): "Using whole genome sequencing of two half-sib affected lambs, their sire, and their two normal dams, a heterozygous C>T transition at OAR10:77593415 (Oar_v3.1) in exon 1 of the fibroblast growth factor 14 (FGF14) gene (c.46C>T) was identified. The c.46C>T transition resulted in a premature stop codon at position 16 of the 247 amino acid FGF14 protein (p.Q16*). PCR and Sanger sequencing was used to genotype an additional 20 clinically affected animals, demonstrating all lambs carried the c.46C>T variant but 1 clinically more severely affected inbred lamb was homozygous (TT)."

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

Clinical features: As reported by Mayhew et al. (2012) "Some lambs were noted to be abnormal at birth, both on home properties and in the experimental flock. They tended to adopt a head and neck extended posture and were slow to get to their feet and suckle when they then became more or less normal. When forced to move, they and other more robust lambs elicited an asymmetric gait, base-wide extensor hypertonia (hypometria) of thoracic limbs and flexor hypertonia (hypermetria) of pelvic limbs. In some there was nystagmus. After several metres of asymmetric ataxic gait they would fall to one side, sometimes adopting a sitting position. Recovery usually occurred in one to several minutes. As lambs aged, it became more difficult to elicit the episodes of dysfunction and by 6 months of age they appeared normal".

Associated gene: