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Duchenne muscular dystrophy: Diagnosis - Coggle Diagram
Duchenne muscular dystrophy: Diagnosis
Muscular dystrophies; clinical characteristics
Delayed ambulation
Frequent falls
Family history, toe walking
Elevated serum creatine kinase
Muscle biopsy
Genetics & pathobiology of Duchenne muscular dystrophy (DMD)
A fatal X-linked recessive, rapidly progressive form of muscular dystrophy
Caused by mutations in the dystrophin (DMD) gene
Muscle damage releases creatine kinase
Prenatal diagnosis
VNTR analysis in known families
Identify XDMD fetal chromosome in a known DMD family
PCR-multiplex PCR on CVS sample
MLPA
Targeted/capture techniques
WES
WGS
Evolution of DMD diagnostics
Muscle Biopsy
Western blot
Dystrophin quantity, quality & localisation
MLPA
Accurate time-efficient detection of genomic deletions & insertions
Determine relative copy number of all exons within a gene simultaneously
Types of mutations known to cause dystrophinopathies
Importance of RNA in diagnosis: understanding genetic variation
Genetic characterisation: Why?
Linking a disease to a gene (s): identifies gene product functions
Monogenic disorders
: (muscular dystrophies), metabolic disorders, inherited motor neuron disease, Alzheimer's, spinal muscular dystrophy
Complex:
Multi-factorial, contribution from multiple loci increase susceptibility to heart disease, motor neuron disease, Alzheimer's, stroke, cancer (s), multiple sclerosis
Knowing genetic basis of disease identifies affected pathways, opportunities for
intervention
Informed reproductive decisions
Prognosis & prediction of disease course
Duchenne muscular dystrophy - opportunities for intervention
Splice Intervention
Antisense oligomers can alter pre-mRNA processing to generate BMD-like mRNA & protein
Remove an exon
Restore reading frame
around a frame-shift mutation
Eight
AO drugs
will treat ~50% of all DMD patients
Different induced isoforms
Genetics & pathobiology of Becker's Muscular Dystrophy (BMD)
Milder allelic disorder
In frame deletions - dystrophin levels >3% normal
Variable phenotype, cardiomyopathy common
Large deletions may be associated with mild/asymptomatic disease