MARCHF6 and benign adult familial myoclonic epilepsy

Benign adult familial myoclonic epilepsy (BAFME) is an autosomal dominant disorder characterized by adult‐onset tremulous hand movement, myoclonus, and infrequent seizures. In a cohort of 12 Japanese pedigrees comprising 51 clinically diagnosed or suspected individuals, intronic TTTCA/TTTTA pentanucleotide repeat expansions in SAMD12 were identified in 49 patients, and nonpathogenic TTTTA expansions in TNRC6A were significantly enriched in affected versus control groups; notably, no expanded repeats in MARCHF6 were observed in any case (PMID:33040085).

No coding or intronic sequence variants in MARCHF6 have been reported in BAFME cohorts, and there are no functional studies linking MARCHF6 perturbation to neuronal hyperexcitability or myoclonus. The absence of pathogenic MARCHF6 repeat expansions in 51 affected individuals refutes a causal role for MARCHF6 in benign adult familial myoclonic epilepsy. Clinically, MARCHF6 genetic testing is not warranted for BAFME diagnosis or carrier screening.

References

• Journal of human genetics • 2021 • DNA analysis of benign adult familial myoclonic epilepsy reveals associations between the pathogenic TTTCA repeat insertion in SAMD12 and the nonpathogenic TTTTA repeat expansion in TNRC6A. PMID:33040085

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