Genetic Epilepsy

Gene: RELN

I don't know

- Six affected individuals carrying missense variants in RELN including
1. Two individuals with compound heterozygous variants
- One of the variants has 26 homozygotes in gnomAD and therefore pathogenicity of this variant is in question
- LoF demonstrated for three of the variants (reduced RELN secretion), except for p.Y1821H which demonstrated an apparently increased RELN secretion (GoF)
2. Two brothers carrying the maternally inherited variant (mother apparently healthy)
- LoF demonstrated for these variants
3. Two individuals de novo for RELN variants
- Dominant negative demonstrated for these variants where secretion of WT-RELN was impaired when co-transfected with mutant constructs in HEK293T cells

Created: 15 Jun 2021, 12:29 a.m. | Last Modified: 15 Jun 2021, 12:29 a.m.

Panel Version: 0.7986

- Two families and two individuals without a family history carrying RELN missense variants
- Three unaffected individuals from one family also carried the variant, leading the authors to suggest potential incomplete penetrance.

Created: 7 Jun 2021, 6:59 a.m. | Last Modified: 7 Jun 2021, 6:59 a.m.

Panel Version: 0.7891

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Pachygyria; Polymicrogyria; Heterotopia

Publications

• Riva et al bioRxiv (pre-print, not peer-reviewed)

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

A temporal lobe epilepsy characterised by autosomal dominant inheritance of focal seizures with prominent auditory symptoms. Variants in this gene accounted for ~20% of ADTLE families in PMID 28142128.

Created: 29 Aug 2020, 4:21 a.m. | Last Modified: 29 Aug 2020, 4:21 a.m.

Panel Version: 0.819

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
{Epilepsy, familial temporal lobe, 7}, MIM# 616436; MONDO:0014639

Publications

• 28142128

I don't know

A heterozygous missense variant segregated with ankylosing spondylitis in a large consanguineous Iranian family (PMID: 32001840).

Created: 3 Aug 2020, 6:26 a.m. | Last Modified: 3 Aug 2020, 6:26 a.m.

Panel Version: 0.3657

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

Phenotypes
ankylosing spondylitis

Publications

• 32001840