Cylindrical spirals in two families: Clinical and genetic investigations
Por:
Beecroft, SJ, Olive, M, Quereda, LG, Gallano, P, Ojanguren, I, McLean, C, McCombe, P, Laing, NG, Ravenscroft, G
Publicada:
1 feb 2020
Resumen:
Cylindrical spirals are a rare ultrastructural finding on muscle biopsy, with fewer than 20 reported cases since its first description in 1979. These structures are sometimes observed with tubular aggregates and are thought to comprise longitudinal sarcoplasmic reticulum. While mutations in genes encoding key components of Ca2+ handling (ORAI1 and STIM1) underlie tubular aggregate myopathy, no causative genes have been associated with cylindrical spirals. Here we describe two families with cylindrical spirals on muscle biopsy with a suspected genetic cause. In one family we identified a known truncating variant in EBF3, previously associated with a neurodevelopmental disorder. The affected individuals in this family present with clinical features overlapping with those described for EBF3 disease. An isolated proband in the second family harbours bi-allelic truncating variants in TTN and her clinical course and other features on biopsy are highly concordant for titinopathy. From experimental studies, EBF3 is known to be involved in Ca2+ regulation in muscle, thus EBF3 dysregulation may represent a novel mechanism of impaired Ca2 + handling leading to cylindrical spirals. Additional cases of EBF3 disease or titinopathy with cylindrical spirals need to be identified to support the involvement of these genes in the pathogenesis of cylindrical spirals. (C) 2020 Elsevier B.V. All rights reserved.
Filiaciones:
Beecroft, SJ:
Univ Western Australia, Ctr Med Res, QEII Med Ctr, Harry Perkins Inst Med Res, Perth, WA, Australia
Olive, M:
Hosp Bellvitge Princeps Espanya, IDIBELL, Dept Neurol, Dept Pathol,Neuropathol Unit, Barcelona 08907, Spain
Hosp Bellvitge Princeps Espanya, IDIBELL, Dept Neurol, Neuromuscular Unit, Barcelona 08907, Spain
Quereda, LG:
Hosp Santa Creu & Sant Pau, Genet Dept, CIBERER, Barcelona 08041, Spain
Gallano, P:
Hosp Santa Creu & Sant Pau, Genet Dept, CIBERER, Barcelona 08041, Spain
Ojanguren, I:
Hosp Badalona Germans Trias & Pujol, Dept Pathol, Badalona 08916, Spain
McLean, C:
Alfred Hlth, Victorian Neuromuscular Lab, Commercial Rd, Prahran, Vic 3181, Australia
McCombe, P:
Univ Queensland, Royal Brisbane & Womens Hosp, Ctr Clin Res, Brisbane, Qld, Australia
Laing, NG:
Univ Western Australia, Ctr Med Res, QEII Med Ctr, Harry Perkins Inst Med Res, Perth, WA, Australia
Ravenscroft, G:
Univ Western Australia, Ctr Med Res, QEII Med Ctr, Harry Perkins Inst Med Res, Perth, WA, Australia
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