Importance of muscle biopsy to establish pathogenicity of DMD missense and splice variants.

Adolescent Adult Biopsy Blood Proteins / genetics Creatine Kinase / blood Diagnosis, Differential Family Humans Male Muscle, Skeletal / pathology Muscular Dystrophy, Duchenne / diagnosis Mutation, Missense RNA Splicing
Becker muscular dystrophy Duchenne muscular dystrophy Missense variants Muscle biopsy Splice variants mRNA studies

Journal

Neuromuscular disorders : NMD
ISSN: 1873-2364
Titre abrégé: Neuromuscul Disord
Pays: England
ID NLM: 9111470

Informations de publication

Date de publication:
12 2019
Historique:
received: 24 01 2019
revised: 29 07 2019
accepted: 22 09 2019
pubmed: 11 11 2019
medline: 10 7 2020
entrez: 11 11 2019
Statut: ppublish

Résumé

A precise genetic diagnosis of a dystrophinopathy has far-reaching implications for affected boys and their families. We present three boys with DMD single nucleotide variants associated with Becker muscular dystrophy presenting with myalgia, reduced exercise capacity, neurodevelopmental symptoms and elevated creatine kinase. The DMD variants were difficult to classify: AIII:1 a synonymous variant in exon 13 c.1602G>A, p.Lys534Lys; BIII:1 an essential splice-site variant in intron 33 c.4674+1G>A, and CII:1 a missense mutation within the cysteine-rich domain, exon 66 c.9619T>C, p.Cys3207Arg. Complementary DNA (cDNA) analysis using muscle-derived mRNA established splice-altering effects of variants for AIII:1 and BIII:1, and normal splicing in CII:1. Western blot analysis demonstrated mildly to moderately reduced dystrophin levels (17.6 - 36.1% the levels of controls), supporting dystrophinopathy as a probable diagnosis. These three cases highlight the diagnostic utility of muscle biopsy for mRNA studies and western blot to investigate DMD variants of uncertain pathogenicity, by exploring effects on splicing and dystrophin protein levels.

Identifiants

DOI: 10.1016/j.nmd.2019.09.013 PMID: 31706698
pubmed: 31706698
pii: S0960-8966(19)31133-2
doi: 10.1016/j.nmd.2019.09.013
pii:
doi:

Substances chimiques

Blood Proteins 0
DMD circulating plasma factor 0
Creatine Kinase EC 2.7.3.2

Types de publication

Case Reports Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

913-919

Informations de copyright

Copyright © 2019 Elsevier B.V. All rights reserved.

Auteurs

Hannah F Jones (HF)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Sydney, New South Wales 2145, Australia; Discipline of Child and Adolescent Health, University of Sydney, Sydney, New South Wales, Australia; Department of Clinical Genetics, Children's Hospital at Westmead, Sydney, New South Wales, Australia.

Samantha J Bryen (SJ)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Sydney, New South Wales 2145, Australia; Discipline of Child and Adolescent Health, University of Sydney, Sydney, New South Wales, Australia.

Leigh B Waddell (LB)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Sydney, New South Wales 2145, Australia; Discipline of Child and Adolescent Health, University of Sydney, Sydney, New South Wales, Australia.

Adam Bournazos (A)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Sydney, New South Wales 2145, Australia; Discipline of Child and Adolescent Health, University of Sydney, Sydney, New South Wales, Australia.

Mark Davis (M)

Department of Diagnostic Genomics, PathWest Laboratory Medicine, QEII Medical Centre, Perth, Western Australia, Australia.

Michelle A Farrar (MA)

Department of Neurology, Sydney Children's Hospital, Sydney, New South Wales, Australia; Discipline of Paediatrics, School of Women's and Children's Health, UNSW Medicine, UNSW Sydney, New South Wales, Australia.

Catriona A McLean (CA)

Anatomical Pathology and Victorian Neuromuscular Laboratory Service, Alfred Health and Monash University, Australia.

David R Mowat (DR)

Centre for Clinical Genetics, Sydney Children's Hospital, Sydney, New South Wales, Australia.

Hugo Sampaio (H)

Department of Neurology, Sydney Children's Hospital, Sydney, New South Wales, Australia.

Ian R Woodcock (IR)

Department of Neurology Royal Children's Hospital, Murdoch Childrens Research Institute and University of Melbourne, Parkville, Victoria, Australia; Murdoch Childrens Research Institute, Melbourne, Victoria, Australia.

Monique M Ryan (MM)

Department of Neurology Royal Children's Hospital, Murdoch Childrens Research Institute and University of Melbourne, Parkville, Victoria, Australia; Murdoch Childrens Research Institute, Melbourne, Victoria, Australia.

Kristi J Jones (KJ)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Sydney, New South Wales 2145, Australia; Discipline of Child and Adolescent Health, University of Sydney, Sydney, New South Wales, Australia; Department of Clinical Genetics, Children's Hospital at Westmead, Sydney, New South Wales, Australia.

Sandra T Cooper (ST)

Kids Neuroscience Centre, The Children's Hospital at Westmead, Sydney, New South Wales 2145, Australia; Discipline of Child and Adolescent Health, University of Sydney, Sydney, New South Wales, Australia. Electronic address: sandra.cooper@sydney.edu.au.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › Importance of muscle biopsy to establish...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Importance of muscle biopsy to establish...
questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Cytodiagnostic › Biopsie › Importance of muscle biopsy to establish...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du sang › Importance of muscle biopsy to establish...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Phosphotransferases (Nitrogenous Group Acceptor) › Creatine kinase › Importance of muscle biopsy to establish...
questionsmedicales.fr › Diagnostic › Diagnostic différentiel › Importance of muscle biopsy to establish...
questionsmedicales.fr › Sciences sociales › Sociologie › Facteurs sociologiques › Famille › Importance of muscle biopsy to establish...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Importance of muscle biopsy to establish...
questionsmedicales.fr › Tissus › Muscles › Muscle strié › Muscles squelettiques › Importance of muscle biopsy to establish...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Dystrophies musculaires › Myopathie de Duchenne › Importance of muscle biopsy to establish...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Mutation faux-sens › Importance of muscle biopsy to establish...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Maturation post-transcriptionnelle des ARN › Épissage des ARN › Importance of muscle biopsy to establish...