Early onset or syndromic epilepsy

Gene: PIP5K1C

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.

Created: 2 May 2024, 1:13 p.m. | Last Modified: 6 May 2024, 9:22 p.m.

Panel Version: 5.6

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (seven unrelated cases and supporting functional evidence) for promoting this gene to green rating in the next GMS review.

Created: 31 Jul 2023, 10:47 a.m. | Last Modified: 31 Jul 2023, 10:47 a.m.

Panel Version: 4.75

Three de novo heterozygous missense variants in PIP5K1C (p.Glu146Lys, p.Tyr205Cys & p.Tyr221Cys) were identified in nine unrelated children exhibiting intellectual disability, developmental delay, acquired microcephaly, seizures, visual abnormalities, and dysmorphic features. Intellectual disability was reported in all nine children and seizures were present in seven children, of which three had developmental and epileptic encephalopathy. In addition, there is functional evidence available, which includes an in vivo zebrafish model that recapitulates the human phenotype (developmental defects affecting the forebrain, including the eyes, as well as craniofacial abnormalities) (PMID:37451268).

This gene has been associated with another phenotype (Lethal congenital contractural syndrome 3, MIM #611369) in both OMIM and Gene2Phenotype, but not yet associated with this neurodevelopmental disorders in either databases.
Sources: Literature

Created: 31 Jul 2023, 10:40 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027

Publications

• 37451268