Presented by Sujitha B Subramaniam 11408044 IV yr Genetic Engineering SRM University DUCHENNE MUSCULAR DYSTROPHY DMD is a recessive Xlinked form of muscular dystrophy which results in muscle degeneration difficulty ID: 593105
Download Presentation The PPT/PDF document "Duchenne Muscular Dystrophy" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Duchenne Muscular Dystrophy
Presented by:Sujitha B Subramaniam11408044IV yr Genetic EngineeringSRM UniversitySlide2
DUCHENNE MUSCULAR DYSTROPHY (DMD) is a recessive X-linked form of muscular dystrophy, which results in muscle degeneration, difficulty
in walking, breathing, and death.Muscular dystrophy - Group of hereditary muscle diseases.
Duchenne Muscular Dystrophy
2Slide3
Duchenne Muscular Dystrophy3
MUSCLE STRUCTURESlide4
EPONYM: DMD is named after the French neurologist
Benjamin Amand Duchenne (1806–1875), who first described the disease in 1861.The Era of Modern Neurology – His findings:
Neural pathways,
The
effect of lesions on these
structures,
Deep tissue biopsy
Nerve
conduction tests (NCS
)
Clinical
photography.
Duchenne Muscular Dystrophy
4Slide5
DMD Research:
Duchenne Muscular Dystrophy5Slide6
SYMPTOMS: The main symptom of Duchenne muscular dystrophy,
A progressive neuromuscular disorder, is muscle weakness associated with muscle wasting.The Other Physical Symptoms Are:
Awkward manner of walking, stepping, or running.
Frequent falls
Fatigue
Difficulty with motor skills (running, hopping, jumping)
Pseudohypertrophy
– Enlarging of calve
Duchenne Muscular Dystrophy
6Slide7
PREVALENCE: DMD has an incidence of 1 in
4,000 newborn males across the world. Diagnosis in boys usually occurs between 16 months and 8 years. INHERITANCE PATTERN: Mother carries the recessive gene and passes it to her child.
Trait
is usually expressed in males only.
Duchenne Muscular Dystrophy
7Slide8
Disease Development with ageDuchenne Muscular Dystrophy
8Slide9
THE GENE:
Duchenne muscular dystrophy is caused by a mutation of the dystrophin gene at locus Xp21.
Duchenne Muscular Dystrophy
9Slide10
Duchenne Muscular Dystrophy10
MOLECULAR MAKEUPGenomic DNA: 2.2 million base pairs.
There are
79
exons
:
which makeup 0.6% of the entire gene.
There are 8 promoters.
N-terminal or
actin
binding sight:
binds
dystrophin
to membranes surrounding striated muscle fiber.
Rod Domain:
contains 24 proteins that repeat and maintain molecular structure.
The
cysteine
-rich domain
The C-terminal:
contains the syntrophin binding sight.Slide11
Dystrophin - protein
Duchenne Muscular Dystrophy11Slide12
GENOTYPE OF DMD
Mutations which affect the DMD gene.
96% are frame-shift mutations.
2-3% are
mutations involving changes in nucleotide.
10-20% of
mutations
occur in the gametocyte.
The most common mutation are repeats of the CAG nucleotides.
Mutations within the
dystrophin
gene can either be inherited or occur spontaneously during
germline
transmission.
Duchenne Muscular Dystrophy
12Slide13
Muscle biopsy:
Complete absence of the protein indicates the condition. DNA test:
The presence of
isoforms
of the gene.
The size of transcript should be 14kb, any change in this can be detected.
The common mutation prone regions
Exon
45-53 and 2 to 20 can be sequenced and mutation can be done
.
DIAGNOSIS:
Duchenne Muscular Dystrophy
13Slide14
Prenatal tests:
The prenatal tests are done to check if the child has inherited the mutated X chromosome from mother, who has a family history of the disease.The samples for the test are got by: Chorionic villus sampling (CVS) 11–14 weeks.
Amniocentesis can be done after 15 weeks.
Fetal
blood sampling can be done at about 18 weeks.
Manual muscle testing
(MMT).
An
electromyography
(EMG) shows
that
weakness is caused by destruction of muscle tissue rather than by
damage
to nerves.Duchenne Muscular Dystrophy
14Slide15
TREATMENT: There
is no current cure for DMD. Treatment is generally aimed at controlling the onset of symptoms to maximize the quality of life, and include the following: Corticosteroids
-
increase energy and strength
.
Mild
,
physical
activity such as swimming is
encouraged.
Physical Therapies.
Orthopedic
appliances.
Splinting and
Orthoses
.
Duchenne Muscular Dystrophy
15
Splinting and Orthoses.Slide16
POSSIBLE COMPLICATIONS: A complete neurological, heart, lung, and muscle exam may show:
a. Duchenne Muscular Dystrophy16
Cardiomyopathy
–
Detoriation
of heart muscle
Muscular atrophy
Scoliosis – Curved spine
Muscle contractures
Muscle deformities
Respiratory disorders
b.
d.
c.
e.Slide17
ONGOING RESEARCH:
Exon
-skipping.
S
tem cell replacement therapy.
A
nalog up-regulation
.
Supportive care.
Gene therapy.
COUNSELING:
Genetic counselling is advised for people with a family history of the disorder.
Duchenne
muscular dystrophy can be detected with about 95% accuracy by genetic studies performed during pregnancy.
Duchenne Muscular Dystrophy
17Slide18
PATIENT ORGANIZATIONS:
Aktion Benni & Co e.v. - Conny and Claus, Germany
Duchenne Muscular Dystrophy
18
CureDuchenne
- Debra and Paul Miller,
Newport Beach, USA.
United Parent Projects Muscular Dystrophy
Duchenne Parent Project, Netherlands.
The
shakthi
foundations, Chennai – India.Slide19
Duchenne Muscular Dystrophy
Thomas
Tonino
- 2
Stan
Groten
- 5
Jayden Hendricks - 3.5
Bram - 2
Maarten
Rooseleers
- 17months
CHILDREN WITH DMDSlide20
Duchenne Muscular Dystrophy
2020
Howard Thomas – San Pedro Sampler
Jonathan – Spine fusion, 3 heart surgery, Lung infection Slide21
Duchenne Muscular Dystrophy
‘LIFE IS SHORT, SO WORK/PLAY HARD’.References:http://www.mja.com.au/www.geneticseducation.nhs.ukwww.nature.com
www.mda.org
www.genomebiology.com
www.ncbi.nlm.nih.gov
www.wikipedia.com