Universität zu Köln

Romeike, Bernd F. M., Becker, Kerstin, Grosskreutz, Julian ORCID: 0000-0001-9525-1424, Schulz, Solveig, Weis, Joachim and Cirak, Sebahattin (2019). A family with limb girdle muscular dystrophy type 1B and multiple exostoses. Clin. Neuropathol., 38 (5). S. 225 - 233. DEISENHOFEN-MUENCHEN: DUSTRI-VERLAG DR KARL FEISTLE. ISSN 0722-5091

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Abstract

Introduction: Next-generation sequencing in cases of hereditary neuromuscular disorders often yields multiple candidate gene variants. Here, we describe a case with mutations in two genes, lamin A/C (LMNA) and exostosin glycosyltransferase 2 (EXT2), which led to hereditary myopathy combined with multiple exostoses. Case history: A 51-year-old German woman with a history of removal of multiple exostoses during childhood presented with proximal limb-girdle muscular dystrophy and a newly diagnosed cardiomyopathy with atrioventricular conduction block. Because her younger son had exostoses and her younger brother had died at age 44 after heart transplantation due to dilated cardiomyopathy, an autosomal dominant inheritance was suspected. Results: Muscle biopsy revealed features of chronic myopathy associated with focal myofibrillar disintegration. Electron microscopy showed myonuclear, myofibrillar, and Z-disc alterations, accumulations of granulofilamenentous material, and a large sporadic osmiophilic inclusion body reminiscent of a nemaline body. Mendeliome and Sanger sequencing detected both a c.1129C>T LMNA mutation of known pathogenicity and a c.1101_1102delAG (E368Kfs*18) truncating EXT2 mutation in the patient and her affected son. Discussion: The clinical. genetic, and muscle biopsy findings suggest that both mutations are pathogenic. The EXT2 mutation was most likely responsible for the multiple exostoses phenotype in mother and son, whereas the myopathy was probably caused by a combined effect of the LMNA and EXT2 mutations.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Romeike, Bernd F. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Grosskreutz, Julian UNSPECIFIED orcid.org/0000-0001-9525-1424 UNSPECIFIED Schulz, Solveig UNSPECIFIED UNSPECIFIED UNSPECIFIED Weis, Joachim UNSPECIFIED UNSPECIFIED UNSPECIFIED Cirak, Sebahattin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-143074
DOI:	10.5414/NP301091
Journal or Publication Title:	Clin. Neuropathol.
Volume:	38
Number:	5
Page Range:	S. 225 - 233
Date:	2019
Publisher:	DUSTRI-VERLAG DR KARL FEISTLE
Place of Publication:	DEISENHOFEN-MUENCHEN
ISSN:	0722-5091
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DILATED CARDIOMYOPATHY; MISSENSE MUTATION; LMNA MUTATIONS; LAMIN; GENE; ONSET; PHENOTYPE; MYOPATHY Multiple languages Clinical Neurology; Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14307