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57. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie (DGNN)

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie

12. - 15.09.2012, Erlangen

Banner: 57. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie

Proteomic characterization of aggregate components in an intrafamilial variable FHL1opathy

Meeting Abstract

  • presenting/speaker Sarah Feldkirchner - Friedrich Baur Institut, München, Germany
  • Maggie Walter - Friedrich Baur Institut, München, Germany
  • Stefan Müller - Central Bioanalytics, Center for Molecular Medicine Cologne, Köln, Germany
  • Christiana Kubny - Friedrich Baur Institut, München, Germany
  • Sabine Krause - Friedrich Baur Institut, München, Germany
  • Wolfram Kress - Institute of Human Genetics, Würzburg, Germany
  • Franz-Georg Hanisch - Central Bioanalytics, Center for Molecular Medicine Cologne, Köln, Germany
  • Benedikt Schoser - Friedrich Baur Institut, München, Germany
  • Joachim Schessl - Friedrich Baur Institut, München, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnOP01

DOI: 10.3205/12dgnn001, URN: urn:nbn:de:0183-12dgnn0011

Veröffentlicht: 11. September 2012

© 2012 Feldkirchner et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Question: FHL1opathies are rare X-linked dominant disorders of muscle with an expanding clinical spectrum associated with given FHL1mutations and encompass the spectrum of myofibrillar myopathies.

Methods: We ascertained two male siblings with a severe and progressive myopathy and protein aggregation in skeletal muscle. Mutation detection was performed by direct sequencing ofFHL1exons. Laser microdissection combined with quantitative mass spectrometry was utilized to identify the composition of the protein aggregates.

Results: We identified a C224W mutation in the fourth LIM-domain of FHL1 in both brothers. The severely progressive course of the disease revealed a striking intrafamilial variability. Protein aggregation and reducing bodies were observed in the muscle biopsy. Using quantitative mass spectrometry we identified the FHL1 protein as the component showing highest increased abundance in the aggregates in both patients.

Conclusions: We report two severely affected brothers with a protein aggregation disorder of the muscle caused by the C224W mutation in theFHL1gene. Of note is the clear identification of reducing bodies in the muscle biopsy samples in FHL1opathy of adults. We describe that the combination of laser microdissection and quantitative mass spectrometry confirms the underlying gene defect by the ratio of the protein content in the aggregates and hereby has a high potential as a new diagnostic tool for identification of causative gene mutations and possibly modifier genes in myofibrillar myopathies.