Movement disorders : official journal of the Movement Disorder Society · 2025
Repeat Expansions with Small TTTCA Insertions in MARCHF6 Cause Familial Myoclonus without Epilepsy.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Kühnel Theresa, Leitão Elsa, Lunzer Renate, Kilpert Fabian, Kaya Sabine, Del Gamba Claudia, Astudillo Kelly, Frucht Steven, Simonetta-Moreau Marion, Bieth Eric, Unterberger Iris, Riboldi Giulietta Maria, Depienne Christel
Аннотация
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.
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.