In other species: chicken , white-tufted-ear marmoset , dog , domestic cat , horse , rabbit , golden hamster , Mongolian gerbil , prairie vole

Categories: Behaviour / neurological phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 104130 (trait) , 117100 (trait) , 121200 (trait) , 121201 (trait) , 125370 (trait) , 132090 (trait) , 132100 (trait) , 132300 (trait) , 159600 (trait) , 182610 (trait) , 203600 (trait) , 208700 (trait) , 220300 (trait) , 226750 (trait) , 226800 (trait) , 226810 (trait) , 226850 (trait) , 254770 (trait) , 254780 (trait) , 254800 (trait) , 266270 (trait) , 267740 (trait) , 270805 (trait) , 301900 (trait) , 310370 (trait) , 545000 (trait) , 600131 (trait) , 600143 (trait) , 600512 (trait) , 600513 (trait) , 600669 (trait) , 601068 (trait) , 245570 (trait)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Considered a defect: yes

Key variant known: yes

Key variant is published: no

Species-specific name: including information about 'Idiopathic Epilepsy, IE'

Molecular basis: Jacinto et al. (2023) investigated a 6-month Holstein heifer with epilepsy: "Whole genome sequencing of the affected heifer identified a private heterozygous splice-site variant in DYRK1B (NM_001081515.1: c.-101-1G>A)... ." The authors "speculate that the identified variant in DYRK1B arose from a de novo mutation ...[and] may be the cause of the observed disease, although [DYRK1B] has not previously been associated with epilepsy in mammals, including humans. ... Further functional studies into DYRK1B's role in epilepsies are needed."

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

Clinical features: Age of onset in affected Hereford animals (occurrence of the first seizure) can be variable, ranging from birth to several months of age. Occurrence and persistence of seizures may be influenced by environmental stressors such as temperature extremes (e.g., extreme cold during calving) or increased physical activity (e.g., processing at vaccination or weaning). Upon initial onset of seizures calves may appear to walk with a stiffened, irregular gait. During seizure episodes individuals will typically lie on their side with all limbs extended in a rigid state. Manual flexing of the limbs is possible, but return to the extended position occurs after release. Seizure episodes may last from several minutes to more than an hour. No anatomic abnormalities or histologic lesions detected. (text kindly provided by Dr J. Beever 4 Feb 2008))

Jacinto et al. (2023) report a single 6 month old Holstein heifer with "epilepsy with focal seizures progressing to generalized seizures ... . The animal was hospitalised for 18 months, during which the seizure frequency was inconstant, ranging from one to four seizures per week and not more than one seizure per day."

Pathology: The Holstein heifer investigated by Jacinto et al. (2023) had brain histopathology "consistent with axonal degeneration and astrocytic gliosis, and the ectopic position of Purkinje cells in the internal granule cell layer."

Genetic testing: A DNA test for an autosomal recessive form of epilepsy in Hereford cattle (idiopathic Epilepsy, shaker calf (Rousseaux et al., 1985 ) has been developed by Dr Jon Beever, Department of Animal Sciences, University of Illinois, but inforamtion about the causal gene or variant have not been published.

Breeds: Hereford (Cattle) (VBO_0000232), Holstein Friesian (Cattle) (VBO_0000239).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below