NEM6, KBTBD13-Related Congenital Myopathy: Myopathological Analysis in 18 Dutch Patients Reveals Ring Rods Fibers, Cores, Nuclear Clumps, and Granulo-Filamentous Protein Material. Issue 4 (7th March 2021)

• Record Type: Journal Article
• Authors: Bouman, Karlijn; Küsters, Benno; De Winter, Josine M; Gillet, Cynthia; Van Kleef, Esmee S B; Eshuis, Lilian; Brochier, Guy; Madelaine, Angeline; Labasse, Clémence; Boulogne, Claire; Van Engelen, Baziel G M; Ottenheijm, Coen A C; Romero, Norma B; Voermans, Nicol C; Malfatti, Edoardo
• Is Part Of: Journal of neuropathology and experimental neurology. Volume 80:Issue 4(2021)
• Page Start: 366
• Page End: 376
• Publication Date: 2021-03-07
• Subjects: Congenital nemaline myopathy type 6 (NEM6) -- Cores -- Electron microscopy -- Granulofilamentous protein material -- KBTBD13 -- Myopathology -- Nuclear clumps -- Rods; Neurology -- Diseases -- Periodicals; Neurology -- Diseases -- Physiopathology -- Periodicals; 616.8047
• DOI: 10.1093/jnen/nlab012
• Languages: English
• ISSNs: 0022-3069

Abstract

Abstract: Nemaline myopathy type 6 (NEM6), KBTBD13-related congenital myopathy is caused by mutated KBTBD13 protein that interacts improperly with thin filaments/actin, provoking impaired muscle-relaxation kinetics. We describe muscle morphology in 18 Dutch NEM6 patients and correlate it with clinical phenotype and pathophysiological mechanisms. Rods were found in in 85% of biopsies by light microscopy, and 89% by electron microscopy. A peculiar ring disposition of rods resulting in ring-rods fiber was observed. Cores were found in 79% of NEM6 biopsies by light microscopy, and 83% by electron microscopy. Electron microscopy also disclosed granulofilamentous protein material in 9 biopsies. Fiber type 1 predominance and prominent nuclear internalization were found. Rods were immunoreactive for α-actinin and myotilin. Areas surrounding the rods showed titin overexpression suggesting derangement of the surrounding sarcomeres. NEM6 myopathology hallmarks are prominent cores, rods including ring-rods fibers, nuclear clumps, and granulofilamentous protein material. This material might represent the histopathologic epiphenomenon of altered interaction between mutated KBTBD13 protein and thin filaments. We claim to classify KBTBD13-related congenital myopathy as rod-core myopathy.