Curation FAME1 SAMD12

Gene SAMD12

Disease FAME1

Inheritance AD

Score

10 + 1.5 = 11.5 / 18

Genetic + experimental = total

Classification

Definitive

Refuted

Moderate

Definitive

Last Updated 08/14/2025

Pubs Reviewed 5

Publication Span 6.84 years

Publication Interval 6.84 years

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.

All criTRia Curations Locus Page

Genetic evidence

Total: 10

Per page

Category	Type	Citation	Score	Details
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.

Experimental evidence

Total: 1.5

Per page

Category	Type	Citation	Score	Details
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.

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.