acorrigan's version from 2017-05-09 20:23


Question Answer
What is the main type of test used for DMD?MLPA is used to assess copy number across all exons of dystrophin
What proportion of cases will this detect?70-85% of folks have exonic deletion or duplication
If del/dup is not detected by MLPA what happens?Sanger sequencing of all exonic regions and their flanking sequences is done to detect point mutations and small indels
What software is used to investigate pathogenicity of a point mutation or indel?Alamut
What's the inheritance mode for DMD/BMD?X-linked recessive
How are MLPA findings confirmed?QF-PCR
Where is dystrophin expressed?Predominantly in skeletal and cardiac muscle
What does dystrophin do?It maintains the structural integrity of the muscle fibre by connecting the basal lamina to the cytoskeleton
What mutations are associated with Becker MD?In frame mutations or those that cause reduced expression
What types of mutations cause DMD?Frameshift & nonsense mutations that cause premature termination & truncated protein, lead to lack of functional protein
What age do symptoms of DMD appear?Around 4 years of age
What are the main symptoms of DMD?Hugely raised serum creatine kinase levels due to muscle wastage, progressive muscle weakness, Gower's sign, difficulty climbing stairs, standing and walking, enlarged calf muscles (actually infiltrated with fat), Muscle weakness in upper limbs, scoliosis, cardiomyopathy, cognitive impairment (~30%)
What age do BMD symptoms appear?Adolescence
What is the average life expectancy for individuals with DMD/BMD?DMD - teens, BMD - fifties or beyond
What types of referrals are received?Standard DMD presentation, older males with milder BMD presentation, females with manifesting characteristics of cardiomyopathy/muscle weakness, females with positive family history are assessed for carrier status, females with affected sons are referred for carrier testing, prenatal samples for known female carriers
What is the most common non-molecular test for DMD/BMD?Serum creatine kinase levels, raised levels are associated with muscle wasting
What is a less common non-molecular test?Muscle biopsy, immunohistochemical assays target dystrophin to demonstrate lack of/reduced expression
What proportion of cases of DMD/BMD are explained by point mutations or indels15-30%
It's not the size of the mutation but the xxxxx that counts....impact upon the reading frame
Why do nonsense mutations cause a severe clinical course?Nonsense cause premature termination, truncated protein, inherently unstable, functional protein levels are severley depleted
DMD has xxx exons....79
What software is used to analyse MLPA results?Gene Mapper
How does MLPA work?Probes target exonic sequence, adjacent probes are ligated to one another, universal fluorescently tagged primers target common sequence on the probes and amplify the ligated sequence, each ligation product has a unique size
What is the treatment for DMD/BMD?No cure, physiotherapy, stretching braces, surgery for scoliosis
Why are corticosteroids used?Strengthen muscle, slow wasting
What happens at night?Machines are required to assist with breathing in later stages of the disease
What treatment is currently being trialled?Exon skipping, mediated by antisense oligonucleotides, this creates an in-frame del dup & can lesser severity of the clinical course
What is one drawback of MLPA?It cannot detect mosaicism.

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