Universität zu Köln

Zou, Yaqun, Zwolanek, Daniela, Izu, Yayoi, Gandhy, Shreya, Schreiber, Gudrun, Brockmann, Knut, Devoto, Marcella, Tian, Zuozhen, Hu, Ying, Veit, Guido ORCID: 0000-0002-6758-2696, Meier, Markus ORCID: 0000-0003-1068-746X, Stetefeld, Joerg ORCID: 0000-0003-1478-3248, Hicks, Debbie, Straub, Volker ORCID: 0000-0001-9046-3540, Voermans, Nicol C., Birk, David E., Barton, Elisabeth R., Koch, Manuel ORCID: 0000-0002-2962-7814 and Boennemann, Carsten G. (2014). Recessive and dominant mutations in COL12A1 cause a novel EDS/myopathy overlap syndrome in humans and mice. Hum. Mol. Genet., 23 (9). S. 2339 - 2353. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2083

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Abstract

Collagen VI-related myopathies are disorders of connective tissue presenting with an overlap phenotype combining clinical involvement from the muscle and from the connective tissue. Not all patients displaying related overlap phenotypes between muscle and connective tissue have mutations in collagen VI. Here, we report a homozygous recessive loss of function mutation and a de novo dominant mutation in collagen XII (COL12A1) as underlying a novel overlap syndrome involving muscle and connective tissue. Two siblings homozygous for a loss of function mutation showed widespread joint hyperlaxity combined with weakness precluding independent ambulation, while the patient with the de novo missense mutation was more mildly affected, showing improvement including the acquisition of walking. A mouse model with inactivation of the Col12a1 gene showed decreased grip strength, a delay in fiber-type transition and a deficiency in passive force generation while the muscle seems more resistant to eccentric contraction induced force drop, indicating a role for a matrix-based passive force-transducing elastic element in the generation of the weakness. This new muscle connective tissue overlap syndrome expands on the emerging importance of the muscle extracellular matrix in the pathogenesis of muscle disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zou, Yaqun UNSPECIFIED UNSPECIFIED UNSPECIFIED Zwolanek, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Izu, Yayoi UNSPECIFIED UNSPECIFIED UNSPECIFIED Gandhy, Shreya UNSPECIFIED UNSPECIFIED UNSPECIFIED Schreiber, Gudrun UNSPECIFIED UNSPECIFIED UNSPECIFIED Brockmann, Knut UNSPECIFIED UNSPECIFIED UNSPECIFIED Devoto, Marcella UNSPECIFIED UNSPECIFIED UNSPECIFIED Tian, Zuozhen UNSPECIFIED UNSPECIFIED UNSPECIFIED Hu, Ying UNSPECIFIED UNSPECIFIED UNSPECIFIED Veit, Guido UNSPECIFIED orcid.org/0000-0002-6758-2696 UNSPECIFIED Meier, Markus UNSPECIFIED orcid.org/0000-0003-1068-746X UNSPECIFIED Stetefeld, Joerg UNSPECIFIED orcid.org/0000-0003-1478-3248 UNSPECIFIED Hicks, Debbie UNSPECIFIED UNSPECIFIED UNSPECIFIED Straub, Volker UNSPECIFIED orcid.org/0000-0001-9046-3540 UNSPECIFIED Voermans, Nicol C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Birk, David E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Barton, Elisabeth R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Manuel UNSPECIFIED orcid.org/0000-0002-2962-7814 UNSPECIFIED Boennemann, Carsten G. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-440018
DOI:	10.1093/hmg/ddt627
Journal or Publication Title:	Hum. Mol. Genet.
Volume:	23
Number:	9
Page Range:	S. 2339 - 2353
Date:	2014
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2083
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TISSUE-SPECIFIC EXPRESSION; CONGENITAL MUSCULAR-DYSTROPHY; COLLAGEN-XII; CONNECTIVE-TISSUE; TENASCIN-X; SOLEUS MUSCLE; DIFFERENTIAL EXPRESSION; SPLICE VARIANTS; SUPPORT OVERLAP; SKELETAL-MUSCLE Multiple languages Biochemistry & Molecular Biology; Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44001