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

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

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Pages (from-to)366-376
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Issue number4
Publication statusPublished - 7 Mar 2021

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