Genetic Epilepsy

Gene: SETD1A

Green List (high evidence)

OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism.

In addition, there are 4 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.

Created: 21 Oct 2020, 10:12 p.m. | Last Modified: 21 Oct 2020, 10:12 p.m.

Panel Version: 0.884

PMID 32346159: Described 15 individuals with de novo SETD1A variants presenting with global developmental delay and/or intellectual disability, subtle facial dysmorphisms, behavioral and psychiatric problems. Examined cellular phenotypes in three patient-derived cell lines with three variants: p.Gly535Alafs*12, c.4582-2_4582delAG, and p.Tyr1499Asp and results suggested that that these variants behave as loss-of-function (LoF) alleles.

Created: 2 Oct 2020, 11:13 p.m. | Last Modified: 2 Oct 2020, 11:13 p.m.

Panel Version: 0.874

PMID: 31197650. Four unrelated families reported: in three, the variants occurred de novo, and in the fourth, it segregated with disease. Some functional data.
Sources: Literature

Created: 4 Jan 2020, 6:02 a.m. | Last Modified: 21 Oct 2020, 10:12 p.m.

Panel Version: 0.884

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epilepsy, early-onset, with or without developmental delay, MIM# 618832; Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM# 619056

Publications

• 31197650
• 32346159