RT Journal Article
T1 Loss of Sarcomeric Scaffolding as a Common Baseline Histopathologic Lesion in Titin-Related Myopathies.
A1 Ávila-Polo, Rainiero
A1 Malfatti, Edoardo
A1 Lornage, Xavière
A1 Cheraud, Chrystel
A1 Nelson, Isabelle
A1 Nectoux, Juliette
A1 Böhm, Johann
A1 Schneider, Raphaël
A1 Hedberg-Oldfors, Carola
A1 Eymard, Bruno
A1 Monges, Soledad
A1 Lubieniecki, Fabiana
A1 Brochier, Guy
A1 Thao Bui, Mai
A1 Madelaine, Angeline
A1 Labasse, Clémence
A1 Beuvin, Maud
A1 Lacène, Emmanuelle
A1 Boland, Anne
A1 Deleuze, Jean-François
A1 Thompson, Julie
A1 Richard, Isabelle
A1 Taratuto, Ana Lía
A1 Udd, Bjarne
A1 Leturcq, France
A1 Bonne, Gisèle
A1 Oldfors, Anders
A1 Laporte, Jocelyn
A1 Romero, Norma Beatriz
AB Titin-related myopathies are heterogeneous clinical conditions associated with mutations in TTN. To define their histopathologic boundaries and try to overcome the difficulty in assessing the pathogenic role of TTN variants, we performed a thorough morphological skeletal muscle analysis including light and electron microscopy in 23 patients with different clinical phenotypes presenting pathogenic autosomal dominant or autosomal recessive (AR) mutations located in different TTN domains. We identified a consistent pattern characterized by diverse defects in oxidative staining with prominent nuclear internalization in congenital phenotypes (AR-CM) (n = 10), ± necrotic/regenerative fibers, associated with endomysial fibrosis and rimmed vacuoles (RVs) in AR early-onset Emery-Dreifuss-like (AR-ED) (n = 4) and AR adult-onset distal myopathies (n = 4), and cytoplasmic bodies (CBs) as predominant finding in hereditary myopathy with early respiratory failure (HMERF) patients (n = 5). Ultrastructurally, the most significant abnormalities, particularly in AR-CM, were multiple narrow core lesions and/or clear small areas of disorganizations affecting one or a few sarcomeres with M-band and sometimes A-band disruption and loss of thick filaments. CBs were noted in some AR-CM and associated with RVs in HMERF and some AR-ED cases. As a whole, we described recognizable histopathological patterns and structural alterations that could point toward considering the pathogenicity of TTN mutations.
YR 2018
FD 2018
LK http://hdl.handle.net/10668/13134
UL http://hdl.handle.net/10668/13134
LA en
DS RISalud
RD Apr 6, 2025