Early onset or syndromic epilepsy

Gene: CHRM1

Comment on list classification: Demoted from Amber to Red to match my review.

Created: 11 Oct 2021, 9:56 a.m. | Last Modified: 11 Oct 2021, 9:56 a.m.

Panel Version: 2.437

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. As there is currently only 1 case with epilepsy this gene has been given a Red rating.

Created: 11 Oct 2021, 9:51 a.m. | Last Modified: 11 Oct 2021, 9:56 a.m.

Panel Version: 2.436

I don't know

PMID: 34212451 - 2 unrelated cases with de novo missense variants (p.Pro380Leu and p.Phe425Ser), one case with early-onset refractory epilepsy, severe disability, and progressive cerebral and cerebellar atrophy, and the second case with mild dysmorphism, global developmental delay, and moderate intellectual disability. In vitro biochemical analyses of p.Pro380Leu demonstrated a reduction in protein levels, impaired cellular trafficking, and defective activation of intracellular signaling pathways.
PMID: 31981491 - an autism spectrum disorder (no other information on phenotype, except ascertained to have severe neurodevelopmental delay) case with a de novo missense variant p.(Arg210Leu)
PMID: 12483218 - null mouse model assessing memory demonstrated selective cognitive dysfunction.
Sources: Literature

Created: 12 Sep 2021, 5:50 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental delay; intellectual disability; autism

Publications

• 34212451
• 31981491
• 12483218