Universität zu Köln

Schessl, Joachim, Bach, Elisa, Rost, Simone, Feldkirchner, Sarah, Kubny, Christiana, Mueller, Stefan, Hanisch, Franz-Georg, Kress, Wolfram and Schoser, Benedikt ORCID: 0000-0002-2757-8131 (2014). Novel recessive myotilin mutation causes severe myofibrillar myopathy. Neurogenetics, 15 (3). S. 151 - 157. NEW YORK: SPRINGER. ISSN 1364-6753

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Abstract

We identified the first homozygous and hence recessive mutation in the myotilin gene (MYOT) in a family affected by a severe myofibrillar myopathy (MFM). MFM is a rare, progressive and devastating disease of human skeletal muscle with distinct histopathological pattern of protein aggregates and myofibrillar degeneration. So far, only heterozygous missense mutations in MYOT have been associated with autosomal dominant myofibrillar myopathy, limb-girdle muscular dystrophy type 1A and distal myopathy. Myotilin itself is highly expressed in skeletal and cardiac muscle and is localized at the Z-disc and therefore interacts in sarcomere assembly. We performed whole-exome sequencing in a German family clinically diagnosed with MFM and identified a homozygous mutation in exon 2, c.16C > G (p.Arg6Gly). Using laser microdissection followed by quantitative mass spectrometry, we identified the myotilin protein as one component showing the highest increased abundance in the aggregates in the index patient. We suggest that the combined approach has a high potential as a new tool for the confirmation of unclassified variants which are found in whole-exome sequencing approaches.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schessl, Joachim UNSPECIFIED UNSPECIFIED UNSPECIFIED Bach, Elisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Rost, Simone UNSPECIFIED UNSPECIFIED UNSPECIFIED Feldkirchner, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Kubny, Christiana UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Hanisch, Franz-Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Kress, Wolfram UNSPECIFIED UNSPECIFIED UNSPECIFIED Schoser, Benedikt UNSPECIFIED orcid.org/0000-0002-2757-8131 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-432937
DOI:	10.1007/s10048-014-0410-4
Journal or Publication Title:	Neurogenetics
Volume:	15
Number:	3
Page Range:	S. 151 - 157
Date:	2014
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1364-6753
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GIRDLE MUSCULAR-DYSTROPHY; LASER MICRODISSECTION; PROTEIN; 1A; COMPONENTS; PHENOTYPE; PATIENT; LGMD1A Multiple languages Genetics & Heredity; Clinical Neurology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43293