Curation FAME8 RAI1

Gene RAI1
Disease FAME8
Inheritance AD
Score

1.5 + 0 = 1.5 / 18

Genetic + experimental = total
Classification
0
18
Refuted
Moderate
Definitive
Last Updated 08/14/2025
Pubs Reviewed 2
Publication Span 0.45 years
Publication Interval 0.45 years
Curator(s) Macayla Weiner, Laurel Hiatt, Harriet Dashnow
Description

FAME8 is an autosomal dominant benign adult familial myoclonic epilepsy caused by an intronic RAI1 TTTTA repeat expansion followed by TTTCA repeat insertion. The locus was reported in a large Malian family, where the expansion co-segregated with disease in affected relatives and TTTCA insertions were absent from Malian controls. RAI1 blood RNA studies did not show altered expression, suggesting RAI1 haploinsufficiency is unlikely; the disease mechanism remains uncertain and likely repeat-dependent.

All criTRia Curations Locus Page

Genetic evidence

Total: 1.5

Category
Type
Citation
Score
Details
Singular Evidence
Probands
PMID:37994247
1.5

One large Malian BAFME8 family: 10 affected and 17 unaffected relatives were studied; RAI1 intron 4 TTTTA expansion with TTTCA insertion was identified by long-read sequencing/RP-PCR, co-segregated with disease, and TTTCA insertions were absent in 200 Malian controls.

Collective Evidence
Computational
PMID:38871700
0

Identified a coding CAG repeat in RAI1 that was computationally predicted to be at risk for expansion based on population variability and that RAI1 is more highly expressed in the brain than other tissues. However, this evidence is not specific to the intronic TTTTA/TTTCA repeat expansion and so was given a score of 0.

Experimental evidence

Total: 0

Category
Type
Citation
Score
Details
Function
Regulatory impact
PMID:37994247
0

Leukocyte RNA levels of RAI1 in six Malian BAFME patients were no different from controls. As no difference was observed, this evidence was given a score of 0.
Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.