Heterozygous loss-of-function variants in SPTAN1 cause an early childhood onset distal myopathy.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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De Winter Jonathan, Van de Vondel Liedewei, Ermanoska Biljana, Monticelli Alice, Isapof Arnaud, Cohen Enzo, Stojkovic Tanya, Hackman Peter, Johari Mridul, Palmio Johanna, Waldrop Megan A, Meyer Alayne P, Nicolau Stefan, Flanigan Kevin M, Töpf Ana, Diaz-Manera Jordi, Straub Volker, Longman Cheryl, McWilliam Catherine A, Orbach Rotem, Verma Sumit, Laine Regina, Donkervoort Sandra, Bonnemann Carsten G, Rebelo Adriana, Züchner Stephan, Grider Tiffany, Shy Michael E, Maystadt Isabelle, Demurger Florence, Cairns Anita, Beecroft Sarah, Folland Chiara, De Ridder Willem, Ravenscroft Gina, Bonne Gisèle, Udd Bjarne, Baets Jonathan
Аннотация
METHODS: Through international collaboration we identified 14 families with distal weakness and heterozygous SPTAN1 loss-of-function variants. Clinical data, electrophysiology, muscle computed tomography or magnetic resonance imaging, and muscle biopsy findings were collected and standardized. SPTAN1 protein, messenger RNA expression analysis and copy DNA sequencing was performed on muscle tissue from 2 participants.
RESULTS: Five families showed autosomal dominant mode of inheritance, whereas in 9 patients the variant was shown to be de novo, including 2 pairs of monozygotic twins. In 2 families, further segregation analysis was not possible. All affected participants presented with early childhood-onset distal weakness and foot abnormalities. Muscle magnetic resonance imaging or computed tomography in 10 patients showed fatty infiltration of the distal lower limb anterior compartment and/or selective involvement of the extensor hallucis longus muscle. Muscle biopsy revealed myopathic changes in 7 patients. Finally, we provide proof for nonsense-mediated decay in muscle tissue derived from 2 patients.
CONCLUSION: We present evidence linking heterozygous SPTAN1 loss-of-function variants to childhood-onset distal myopathy in 14 unrelated families.