Universität zu Köln

Bello, Luca ORCID: 0000-0002-3075-6525, Morgenroth, Lauren P., Gordish-Dressman, Heather, Hoffman, Eric P., McDonald, Craig M. and Cirak, Sebahattin (2016). DMD genotypes and loss of ambulation in the CINRG Duchenne Natural History Study. Neurology, 87 (4). S. 401 - 410. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1526-632X

Full text not available from this repository.

Abstract

Objective:To correlate time to loss of ambulation (LoA) and different truncating DMD gene mutations in a large, prospective natural history study of Duchenne muscular dystrophy (DMD), with particular attention to mutations amenable to emerging molecular treatments.Methods:We analyzed data from the Cooperative International Neuromuscular Research Group Duchenne Natural History Study for participants with DMD single- or multi-exon deletions or duplications with defined exon boundaries (n = 186), or small mutations identified by sequencing (n = 26, including 16 nonsense point mutations). We performed a time-to-event analysis of LoA, a strong indicator of overall disease severity, adjusting for glucocorticoid treatment and genetic modifiers.Results:Participants with deletions amenable to skipping of exon 44 had later LoA (median 14.8 years, hazard ratio 0.31, 95% confidence interval 0.14-0.69, p = 0.004). Age at LoA did not differ significantly in participants with deletions amenable to exon 45, 51, and 53 skipping, duplications, and small rearrangements. Nonsense mutation DMD also showed a typical median age at LoA (11.1 years), with a few outliers (ambulatory around or after 16 years of age) carrying stop codons within in-frame exons, more often situated in the rod domain.Conclusions:As exon 44 skipping-amenable DMD has a later LoA, mutation-specific randomization and selection of placebo groups are essential for the success of clinical trials.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bello, Luca UNSPECIFIED orcid.org/0000-0002-3075-6525 UNSPECIFIED Morgenroth, Lauren P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gordish-Dressman, Heather UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffman, Eric P. UNSPECIFIED UNSPECIFIED UNSPECIFIED McDonald, Craig M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cirak, Sebahattin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-269605
DOI:	10.1212/WNL.0000000000002891
Journal or Publication Title:	Neurology
Volume:	87
Number:	4
Page Range:	S. 401 - 410
Date:	2016
Publisher:	LIPPINCOTT WILLIAMS & WILKINS
Place of Publication:	PHILADELPHIA
ISSN:	1526-632X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MUSCULAR-DYSTROPHY; NONSENSE MUTATION; CLINICAL-TRIALS; RESTORATION; DRISAPERSEN; DELETIONS; ATALUREN; SAFETY Multiple languages Clinical Neurology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26960