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Amyloidose bei Muskeldystrophie

Amyloidosis in muscular dystrophy

  • Schwerpunkt: Amyloid und Amyloidosen
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Zusammenfassung

Mutationen im Gen für Dysferlin (DYSF) verursachen Gliedergürtelmuskeldystrophie 2B (LGMD2B) und Miyoshi-Myopathie (MM). Wir konnten 8 Patienten mit vermuteter LGMD2B phänotypisch, genotypisch und histologisch untersuchen. Mutationen im Dysferlin-Gen wurden bei allen Patienten gefunden, in 4 Muskelpräparaten waren sarkolemmale sowie interstitielle Amyloidablagerungen vorhanden. Die Amyloid-assoziierten Mutationen lagen alle im N-terminalen Bereich des Dysferlin-Gens, und Dysferlin war eine Komponente der Amyloidablagerungen. Die Dysferlin-defiziente Muskeldystrophie ist die erste Muskeldystrophie, bei der Amyloid eine Rolle spielt. Diese Tatsache muss bei der Entwicklung von Therapieansätzen beachtet werden. Der Einfluss der Amyloidablagerungen im Skelettmuskel auf die Pathogenese der Erkrankung sowie die mögliche Beteiligung anderer Organe im fortgeschrittenen Verlauf sind noch unklar.

Abstract

Mutations in the gene encoding dysferlin (DYSF) cause limb-girdle muscular dystrophy 2B (LGMD2B) and Miyoshi myopathy (MM). We were able to examine eight patients suspected of LGMD2B clinically, histochemically. The genotype was determined in every case. We found sarcolemmal and interstitial amyloid deposits in four muscle sections. All of the mutations associated with amyloid were located in the N-terminal region of dysferlin, and dysferlin clearly proved to be a component of the amyloid deposits. Dysferlin-deficient muscular dystrophy is the first muscular dystrophy in which amyloidosis is involved. This fact must be considered in the process of developing therapeutic strategies. The influence of the amyloid deposits on the pathogenesis of the disease and the possible involvement of other organs in the progressive course are as yet unclear.

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Danksagung

Diese Arbeit wurde finanziell unterstützt von der Deutschen Forschungsgemeinschaft (DFG; Sp 1152-8/1, S.S.) und der Europäischen Union (EU FPG EURAMY, C.R.).

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Authors and Affiliations

  1. Abteilung für Myologie, Experimental and Clinical Research Center (ECRC), Charité-Universitätsmedizin Berlin und Max-Delbrück-Centrum Berlin, Lindenberger Weg 80, 13125, Berlin, Deutschland

    M. Carl & S. Spuler

  2. Institut für Pathologie, Charité-Universitätsmedizin Berlin, Berlin, Deutschland

    C. Röcken

Authors
  1. M. Carl
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  2. C. Röcken
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  3. S. Spuler
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Correspondence to M. Carl.

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Carl, M., Röcken, C. & Spuler, S. Amyloidose bei Muskeldystrophie. Pathologe 30, 235–239 (2009). https://doi.org/10.1007/s00292-009-1129-0

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  • DOI: https://doi.org/10.1007/s00292-009-1129-0

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