Pseudoexon activation increases phenotype severity in a Becker muscular dystrophy patient

K. Greer; K. Mizzi; E. Rice; L. Kuster; R.A. Barrero; M.I. Bellgard; B.J. Lynch; A.R. Foley; E. O Rathallaigh; S.D. Wilton; S. Fletcher

doi:10.1002/mgg3.144

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Pseudoexon activation increases phenotype severity in a Becker muscular dystrophy patient

Journal article

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Peer reviewed

Pseudoexon activation increases phenotype severity in a Becker muscular dystrophy patient

K. Greer, K. Mizzi, E. Rice, L. Kuster, R.A. Barrero, M.I. Bellgard, B.J. Lynch, A.R. Foley, E. O Rathallaigh, S.D. Wilton, …

Molecular Genetics & Genomic Medicine, Vol.3(4), pp.320-326

2015

DOI: https://doi.org/10.1002/mgg3.144

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Abstract

We report a dystrophinopathy patient with an in-frame deletion of DMD exons 45–47, and therefore a genetic diagnosis of Becker muscular dystrophy, who presented with a more severe than expected phenotype. Analysis of the patient DMD mRNA revealed an 82 bp pseudoexon, derived from intron 44, that disrupts the reading frame and is expected to yield a nonfunctional dystrophin. Since the sequence of the pseudoexon and canonical splice sites does not differ from the reference sequence, we concluded that the genomic rearrangement promoted recognition of the pseudoexon, causing a severe dystrophic phenotype. We characterized the deletion breakpoints and identified motifs that might influence selection of the pseudoexon. We concluded that the donor splice site was strengthened by juxtaposition of intron 47, and loss of intron 44 silencer elements, normally located downstream of the pseudoexon donor splice site, further enhanced pseudoexon selection and inclusion in the DMD transcript in this patient.

Details

Title: Pseudoexon activation increases phenotype severity in a Becker muscular dystrophy patient
Authors/Creators: K. Greer (Author/Creator) - Murdoch University
K. Mizzi (Author/Creator) - The University of Western Australia
E. Rice (Author/Creator) - The University of Western Australia
L. Kuster (Author/Creator) - The University of Western Australia
R.A. Barrero (Author/Creator) - Murdoch University
M.I. Bellgard (Author/Creator) - Murdoch University
B.J. Lynch (Author/Creator) - Temple Street Children's University Hospital
A.R. Foley (Author/Creator) - Temple Street Children's University Hospital
E. O Rathallaigh (Author/Creator)
S.D. Wilton (Author/Creator) - Murdoch University
S. Fletcher (Author/Creator) - Murdoch University
Publication Details: Molecular Genetics & Genomic Medicine, Vol.3(4), pp.320-326
Publisher: Wiley
Identifiers: 991005543329207891
Copyright: © 2015 The Authors
Murdoch Affiliation: Centre for Comparative Genomics
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.255 Musculoskeletal Disorders; 1.255.628 Duchenne Muscular Dystrophy
Web Of Science research areas: Genetics & Heredity
ESI research areas: Molecular Biology & Genetics