Early onset or syndromic epilepsy
Gene: PIP5K1C
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: LiteratureCreated: 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
Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Tag Q3_23_promote_green tag was added to gene: PIP5K1C.
Phenotypes for gene: PIP5K1C were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027
gene: PIP5K1C was added gene: PIP5K1C was added to Early onset or syndromic epilepsy. Sources: Literature Mode of inheritance for gene: PIP5K1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PIP5K1C were set to 37451268 Phenotypes for gene: PIP5K1C were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 Review for gene: PIP5K1C was set to GREEN