Tbilisi State medical university - USMD - Genetics

1. Lasha Chkhikvadze.
USMD 2024

2. MUSCULAR DYSTROPHY
Bad Nourishment

3. Dystrophin gene
• Largest known human gene
• Xp 21.2
• 2 million base pair in length
• 79 exons
• Encodes dystrophin
• Used for movement –
skeletal muscles
• In heart – cardiac muscles
• In brain nerve cells

4. Dystrophin gene mutation
• High chance of mutation
during meiosis
• Deletions/duplications (2/3)
• Point mutations (1/3)

5. Deletion Hotspots
• Central region – in exon 44-53
• 5’ region – in exon 3-21
increased numbers of exon del/dup events could
be caused by extended exon interval length.

6. X-LINKED RECESSIVE
XY XX
Males Females
nonfuntional nonfunctionalfunctional

7. X-INACTIVATION IN FEMALES
asymptomatic
Manifesting
carriers

8. NO dystrophin No stable sarcolemma Increased release of
creatinine kinase into
serum
Increased Ca+2
efflux into the cellCell death
Muscle
regeneration
Muscle
atrophy

9. Age 3-5 Age 6-9 Age: 9-13
• Symptoms appear
• Struggle to sit or
stand independently
• Starts walking later
• Weakness in legs and
pelvic muscles
• Calf (large)
pseudohypertrophy
cause them to
waddle
• Difficult to climb
stairs
• Muscles begin
to waste
• Gower’s sign
• Learning
difficulties
• No longer able to
walk
• Short stature
Age: 13+
• Reduced bone
density
• Reduced cardiac
and lung
function
• Scoliosis
• Cardiomyopathy
– enlarged heart
Age: 19+
• Dependent
on ventilator
or respirator
• In need of
tracheotomy
Age: mid 20s
• heart failure
• Breathing complication

10. DIAGNOSIS
• raised creatine kinase enzymes in the blood
• Detection of mutation in dystrophin gene by:
-DNA test
-Western blot – MLPA
• Muscle biopsy – to check stain for dystrophin

11. Treatment - no treatment…
• Glucocorticoids – slow the degeneration
Side effects: weight gain, cataracts, high blood pressure, face
puffiness, osteoporosis.
• Physical therapy and conditioning – improve
quality of life, but do not reverse the process.
• Exondys 51 (eteplirsen) – approved in 2016 – dystrophin
expression via read-through.
• Dasatinib – cancer drug – kinase inhibitor.
• Embryonic stem cell transplantation.

12. CASE
Mary is a 26 year old pregnant woman who referred to your office by her OB/GYN.
Mary explains that her sister’s, Anna’s son , Nick, who is 8 years old, has recently been diagnosed with
DMD. However, Anna has never experienced any muscular problems and her husband is absolutely
healthy too. Mary also recalls her uncleJohn who died at the age of 23 due to developmental disorder.
She also knows that her mothers cousin George died for the same reason.
1) Draw the pedigree
2) What is the chance that Mary is a carrier?
3) What are you expecting to detect in Nick’s blood test?
4) If Mary is a carrier, what's’ the chance that her son/daughter will be affected?

13. 2) 50% 3) Elevated kinase 4)50%

14. Thank you!