Genetic Epilepsy

Gene: ATP6V1A

Green List (high evidence)

No clear gen-phen correlation, de novo is predominant for AD DEE. Fig 2B in Vogt (2020) visualises distribution.
Carrier parents of patients with AR disase are unaffected.

Both GOF and LOF mechanism described

DEE patients in Fassio 2018
GoF - p.D349 demonstrated this with an increased proton pumping in intracellular organelles
LoF - p.D100Y showed this with decreased expression of protein and reduced levels of lysosomal markers
mechanism not established for AD disease, Fassio had conflicting results across assays.
Cutis laxa patients in Damme 2017
LoF - homozygous variants (p.R338C, p.G72D) identified in cutis lava patients seem to disrupt stabilising interactions within or b/w different subunits of the nucleotide-binding domain
LOF looks established for AR disease

Created: 19 May 2022, 2:07 a.m. | Last Modified: 19 May 2022, 2:07 a.m.

Panel Version: 0.14532

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Cutis laxa, autosomal recessive, type IID MIM#617403; Developmental and epileptic encephalopathy 93 MIM#618012

Publications

• 29668857
• 28065471
• 33320377

Green List (high evidence)

Monoallelic variants associated with Epileptic encephalopathy, infantile or early childhood, 3 618012 and biallelic variants associated with Cutis laxa, autosomal recessive, type IID 617403. Both phenotypes include seizures.
Sources: Expert list

Created: 21 Jan 2020, 6:14 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Epileptic encephalopathy, infantile or early childhood, 618012; Cutis laxa, type IID, 617403

Publications

• 29668857
• 28065471

Variants in this GENE are reported as part of current diagnostic practice