NEM6, KBTBD13-Related Congenital Myopathy: Myopathological Analysis in 18 Dutch Patients Reveals Ring Rods Fibers, Cores, Nuclear Clumps, and Granulo-Filamentous Protein Material.

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.

• Authors: Karlijn Bouman, Benno Küsters, Josine M De Winter, Cynthia Gillet, Esmee S B Van Kleef, Lilian Eshuis, Guy Brochier, Angeline Madelaine, Clémence Labasse, Claire Boulogne, Baziel G M Van Engelen, Coen A C Ottenheijm, Norma B Romero, Nicol C Voermans, Edoardo Malfatti
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 80 Issue 4 Pg. 366-376 (03 22 2021) ISSN: 1554-6578 [Electronic] England
• PMID: 33693846 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 American Association of Neuropathologists, Inc. All rights reserved.

Chemical References

• KBTBD13 protein, human
• Muscle Proteins

Topics

• Adult
• Aged
• Female
• Humans
• Male
• Middle Aged
• Muscle Fibers, Skeletal (pathology)
• Muscle Proteins (genetics)
• Myopathies, Nemaline (epidemiology, genetics, pathology)
• Netherlands (epidemiology)