FAME1_SAMD12
- Gene
- SAMD12
- Disease
- FAME1
- Inheritance
- AD
- Classification
- Definitive
- Total Score
- 11.5
- Publications Reviewed
- 5
- Publication Span
- 6.84 years
- Last Updated
- 08/14/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt
Description
Intronic SAMD12 pentanucleotide repeat expansions involving pathogenic TTTCA insertion with accompanying TTTTA expansion cause autosomal dominant familial adult myoclonic epilepsy type 1 (FAME1/FCMTE1). Multiple studies report affected families across Asian populations, segregation with disease, absence of the TTTCA insertion from controls, computational and long-read detection of the expansion, length-dependent genotype-phenotype correlations, and neuronal UUUCA RNA foci supporting RNA-mediated toxicity.
Genetic evidence
Total: 10
| Singular Evidence | Probands | PMID:39569876 | 6 | Targeted long-read sequencing was performed in 77 FCMTE1 patients from 23 pedigrees; 73 SAMD12 (TTTTA)exp(TTTCA)exp alleles passed quality control for genotype analysis. |
| Collective Evidence | Allele | PMID:39569876 | 2 | (TTTCA)exp counts in 73 FCMTE1 patients were inversely correlated with age at onset of cortical tremor and epilepsy, and increased during parental transmission, supporting a length-dependent pathogenic effect. |
| Collective Evidence | Computational | PMID:32203200 | 0.5 | Whole-genome sequencing repeat-expansion tools detected the SAMD12 TTTCA expansion in affected individuals from Sri Lankan and Indian FAME families and not in controls; RP-PCR validated the calls. |
| Collective Evidence | Segregation | PMID:30194086 PMID:29939203 | 1.5 | PMID:30194086 reported complete cosegregation of SAMD12 TTTTA and inserted TTTCA expansions with FCMTE in a Chinese family, with additional cases in two families. PMID:29939203 reported cosegregation of the SAMD12 (TTTCA)n insertion in 18 Chinese pedigrees and absence in controls. |
4 rows
Experimental evidence
Total: 1.5
| Function | Biochemical function | PMID:29507423 | 1 | FISH of autopsied brains from SAMD12 expansion carriers showed UUUCA-containing RNA foci in cortical neurons and Purkinje cells, supporting repeat RNA-mediated toxicity. |
| Function | Regulatory impact | PMID:29507423 | 0.5 | PMID 29507423 supports reduced SAMD12 protein levels in patient brains. |
2 rows
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.