Chromosome 5q14.3 deletions – deletions within a region of the long arm of chromosome 5 – cause intellectual disability, epilepsy, dysmorphisms (abnormal differences in body structure), structural brain abnormalities, and hypotonia (low muscle tone.)
Seizure types found in 5q14.3 deletions typically include myoclonic seizures, infantile onset of febrile seizures, and infantile spasms. Common structural brain abnormalities include decreased white matter volume, periventricular heterotopia, and polymicrogyria. These are all the result of abnormal brain development prior to birth.
Previous studies have found that deletion of the MEF2C gene – located within the 5q14.3 region – causes many of the epilepsy symptoms in these patients. However, there are some patients with 5q14.3 deletions who have epilepsy – specifically, myoclonic seizures – although the MEF2C gene itself is not deleted. This implies that there are other genes within this region that are also contributing to the epilepsy symptoms.
This article shows that loss of the ADGRV1 gene – another gene located within the 5q14.3 region – may also cause the epilepsy symptoms. This hypothesis is supported by 4 patients with 5q14.3 deletions without MEF2C loss. These patients exhibited a wide range of seizure types, all of which included myoclonic seizures. While none of these patients exhibited MEF2C loss each patient did have loss of ADGRV1. This suggests that ADGRV1 loss may also be contributing to the seizure symptoms of a 5q14.3 deletion.
To test if loss of ADGRV1 causes epilepsy, the authors examined a group of 95 patients with epilepsy and myoclonic seizures without chromosomal abnormalities. ADGRV1 mutations that resulted in loss of gene function were found in 6 of these 95 patients. This confirms that ADGRV1 may be responsible for 6% of myoclonic epilepsies.
Based on the current data, loss of ADGRV1 may be an important factor in epilepsy symptoms in patients with 5q14.3 deletions. Furthermore, it suggests that multiple genes in the 5q14.3 region outside of MEF2C may be responsible for causing epilepsy if lost. Future research on the roles of these genes may result in better treatment options for the specific epilepsy symptoms.
Myers, et al. “ ADGRV1 is implicated in myoclonic epilepsy”. Epilepsia. 2018, v. 59 (2), 381-388.