Genetic Epilepsy

Gene: PRICKLE2

I don't know

PMID: 34092786 (2021): Reporting on six individuals from 4 unrelated families. One family has a segregating frameshift variant across 3 generations (p.Ser429Thrfs*56) - 17yo with diagnosed epilepsy, 41yo with suspected epilepsy without diagnosis, and 68yo with no seizures and normal EEGs, but episodes of presumed involuntary movement of extremities. Remaining three individuals are all unrelated. 1x de novo p.Thr227Arg with diagnosed epilepsy. 1x de novo p.Pro41Leu with suspected epilepsy without diagnosis. 1x de novo p.Arg72* with no seizures and normal EEGs, but staring episodes.

Previous literature sees conflicting interpretations of compound heterozygous variants p.[Arg148His;Val153Ile], with the most recent paper maintaining it is associated with epilepsy. (PMID: 21276947 (2011); 26942291 (2016); 26942292 (2016))

Created: 21 Dec 2023, 4:38 a.m. | Last Modified: 21 Dec 2023, 4:38 a.m.

Panel Version: 0.2094

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Epilepsy

Publications

• 34092786
• 21276947
• 26942291
• 26942292

I don't know

LIMITED by ClinGen, however experimental evidence appears not to have been considered.

Created: 27 Dec 2023, 4:59 a.m. | Last Modified: 27 Dec 2023, 5:10 a.m.

Panel Version: 0.2104

Six subjects from four unrelated families with neurodevelopmental delay, behavioural difficulties and epilepsy had heterozygous variants, either de novo or segregating with disease. Two missense were de novo, c.122 C>T; p.(Pro41Leu) and c.680C>G; p.(Thr227Arg); one nonsense variant was de novo (c.214 C>T; p.(Arg72*); and one frameshift variant segregated with the disorder in three affected females (c.1286_1287delGT; p.(Ser429Thrfs*56)). Loss-of-function (homozygous) variants have been shown to cause seizures in flies; and both heterozygous and homozygous mice have shown behavioral abnormalities including altered social interaction, learning abnormalities, and behavioral inflexibility (PMID: 21276947).
Sources: Literature

Created: 6 Sep 2021, 8:35 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder; global developmental delay; behavioural difficulties ± epilepsy; autistic features; attention deficit hyperactive disorder; psychiatric symptoms

Publications

• 34092786

Green List (high evidence)

Six subjects from four unrelated families with neurodevelopmental delay, behavioural difficulties and epilepsy had heterozygous variants, either de novo or segregating with disease.
Two missense were de novo, c.122 C>T; p.(Pro41Leu) and c.680C>G; p.(Thr227Arg); one nonsense variant was de novo (c.214 C>T; p.(Arg72*); and one frameshift variant segregated with the disorder in three affected females (c.1286_1287delGT; p.(Ser429Thrfs*56)).

Loss-of-function (homozygous) variants have been shown to cause seizures in flies; and both heterozygous and homozygous mice have shown behavioral abnormalities including altered social interaction, learning abnormalities, and behavioral inflexibility (PubMed: 21276947).

Created: 6 Sep 2021, 5:48 a.m. | Last Modified: 6 Sep 2021, 6:11 a.m.

Panel Version: 0.9088

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder, global developmental delay, behavioural difficulties ± epilepsy, autistic features, and attention deficit hyperactive disorder.

Publications

• PMID: 34092786