SAMD12 Repeat Expansion Testing
Description
Pathogenic pentanucleotide TTTCA repeat expansions within the fourth intron of the SAMD12 gene have been associated with autosomal dominant familial adult onset myoclonic epilepsy 1 (FAME1).
Pathogenicity is dependent upon TTTCA repeat length according to the following ranges 1-3:
Normal Alleles | Mutable Normal Alleles | Intermediate/Uncertain Alleles | Reduced Penetrance Alleles | Full Penetrance Alleles |
0 contiguous TTTCA repeats | - | 3-9 contiguous TTTCA repeats | - | 400 or more pentanucleotide repeats (with at least 10 TTTCA repeats)* ** |
*Rare event of onset in teen years has been described 4.
** Both longer or homozygous repeats are associated with an earlier age of onset, and homozygous expansions are additionally associated with a more severe phenotype 4. Some publications suggest that pathogenic alleles are unstable and tend to expand in subsequent generations, with some evidence suggesting greater expansion upon maternal transmission 5-7.