SAMD12 – Familial Adult Myoclonic Epilepsy Type 1

Familial adult myoclonic epilepsy type 1 (FCMTE1) is an autosomal dominant neurodegenerative disorder characterized by cortical myoclonic tremors and generalized seizures (PMID:37890330). A pathogenic (TTTCA)n repeat insertion in intron 4 of SAMD12 has been identified as the causal allele in a single multigenerational family, with only one proband and his affected relatives reported to carry this expansion (PMID:37890330). The variant is absent from population databases and co-segregates with disease in the kindred, but no formal segregation counts are provided.

An induced pluripotent stem cell (iPSC) line (ZJUi013-A) derived from patient fibroblasts harboring the intronic (TTTCA)n expansion was established using Sendai virus reprogramming (PMID:37890330). This model conserves the disease-relevant repeat insertion and offers a platform for investigating SAMD12-mediated neuronal dysfunction and for high-throughput drug screening. However, no in vivo models, rescue experiments, or mechanistic assays have yet been reported. Additional studies are needed to assess the impact of the repeat on SAMD12 transcript processing and to validate pathogenicity in cellular or animal systems. Key take-home: Preliminary genetic and cellular data support further evaluation of SAMD12 intronic repeat expansions in FCMTE1 and justify genetic testing in affected families.

References

• Stem cell research • 2023 • Generation of an induced pluripotent stem cell line (ZJUi013-A) from a Familial cortical myoclonic tremor with epilepsy type 1 patient carrying (TTTCA)n insertion in the SAMD12 gene. PMID:37890330

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