{"doi":"10.1002/mds.30192","title":"Repeat Expansions with Small <scp>TTTCA</scp> Insertions in <scp><i>MARCHF6</i></scp> Cause Familial Myoclonus without Epilepsy","abstract":"BACKGROUND: Familial adult myoclonus epilepsy (FAME) is a rare autosomal dominant disorder caused by the same intronic TTTTA/TTTCA repeat expansion in seven distinct genes. TTTTA-only expansions are benign, whereas those containing TTTCA insertions are pathogenic. OBJECTIVE: We investigated the genetic basis of dominant cortical myoclonus without seizures in two unrelated families. METHODS: Repeat-primed polymerase chain reaction (PCR), long-range PCR, and nanopore sequencing were used to detect and characterize expansions at known FAME loci. RESULTS: We identified a novel repeat expansion in MARCHF6, comprising 388 to 454 elongated TTTTA repeats and 5 to 11 TTTCA repeats at the 3'-terminus, segregating with cortical myoclonus in 8 affected individuals. This configuration shows meiotic stability but low-level somatic variability in blood. We observed an inverse correlation between the number of TTTCA repeats and the age at myoclonus onset. CONCLUSIONS: These findings indicate that as little as five TTTCA repeats combined with expanded TTTTA repeats can cause cortical myoclonus without epilepsy, highlighting the potential mechanisms underlying FAME pathophysiology. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","journal":"Movement Disorders","year":2025,"id":543690,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9609,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":672792,"name":"Elsa Leitão","orcid":"0000-0001-5051-9714","position":1,"is_corresponding":false},{"id":1434017,"name":"Renate Lunzer","orcid":null,"position":2,"is_corresponding":false},{"id":242542,"name":"Fabian Kilpert","orcid":"0000-0001-6401-2180","position":3,"is_corresponding":false},{"id":869239,"name":"Sabine Kaya","orcid":null,"position":4,"is_corresponding":false},{"id":1433679,"name":"Claudia Del Gamba","orcid":"0000-0003-3408-7426","position":5,"is_corresponding":false},{"id":818399,"name":"Kelly Astudillo","orcid":"0000-0002-5697-0968","position":6,"is_corresponding":false},{"id":1434018,"name":"S.J. Frucht","orcid":null,"position":7,"is_corresponding":false},{"id":1027876,"name":"M. Simonetta‐Moreau","orcid":"0000-0002-2278-0410","position":8,"is_corresponding":false},{"id":1433680,"name":"Éric Bieth","orcid":"0000-0003-3126-5493","position":9,"is_corresponding":false},{"id":1433681,"name":"Iris Unterberger","orcid":"0000-0001-6408-5777","position":10,"is_corresponding":false},{"id":661645,"name":"Giulietta Riboldi","orcid":"0000-0003-0322-5718","position":11,"is_corresponding":false},{"id":323120,"name":"Christel Depienne","orcid":"0000-0002-7212-9554","position":12,"is_corresponding":false},{"id":868566,"name":"Theresa Kühnel","orcid":"0000-0003-0629-3521","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-19T02:53:08.338070Z","pmid":"40200849","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}