Early-onset Dementia

Gene: CST3

I don't know

Single founder variant.

Created: 10 Mar 2021, 10:10 a.m. | Last Modified: 10 Mar 2021, 10:10 a.m.

Panel Version: 0.133

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on list classification: Cognitive decline is a feature of CST3-leukodystrophy

Created: 1 Apr 2024, 7:30 a.m. | Last Modified: 1 Apr 2024, 7:30 a.m.

Panel Version: 1.10

New gene-disease association: 16 patients from 8 leukodystrophy families carrying one of four different stop-gain or frameshift dominant variants in the C-terminal (in the NMD-exclusion zone) of the CST3 gene. Suggested mechanism of disease by rendering the protein more prone to aggregation. The clinical phenotype consists of recurrent episodes of hemiplegic migraine associated with transient unilateral focal deficits and slowly progressing motor symptoms and cognitive decline in mid-old adult ages. Clinical & radiological features differ from Cerebral Amyloid Angiopathy.

Created: 1 Apr 2024, 7:28 a.m. | Last Modified: 1 Apr 2024, 7:28 a.m.

Panel Version: 1.9

A single missense variant L68Q causes Icelandic-type CAA, where brain haemorrhage is main presenting feature of the condition. Progressive multi-infarct dementia has been reported in at least 17 cases. Dementia has been reported as the presenting feature in 2 cases from the same family. The gene has also been reported as an Alzheimer's disease susceptibility loci, but there is modest risk associated with the homozygote (rs1064039) minor allele genotype, combined OR 1.6.
Sources: Expert list

Created: 19 Aug 2020, 6:31 a.m. | Last Modified: 19 Aug 2020, 6:32 a.m.

Panel Version: 0.58

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cerebral amyloid angiopathy MIM#105150; leukodystrophy MONDO:0019046

Publications

• 22435454
• 8866434
• 2602413
• 8108423
• 38489591

Mode of pathogenicity
Other