Transcript SMA Geneticsx

GENETICS AND ITS RELATION
TO NEUROMUSCULAR
DISEASES
By: Isam Adam, Jason Fong, Cody Boehner, Ella Dehestani, and Anissa
Santiago
RATIONALE AND OBJECTIVES
• From the personal experience of one of our group members, our attention is
drawn to the topic of neuromuscular diseases, primarily spinal muscular
atrophy, and the relation between such diseases and genetics
• We wish to identify the genetic causes of various neuromuscular diseases
and draw connections between the genome and the disease
• We expect to see mutated exons in the presence of neuromuscular diseases,
such that the affected gene is altered in some way that it is unable to
properly encode for the normal protein, failing to sustain regular cell
processes
FINDINGS
• In our presentation, we will be exploring three different types of
neuromuscular diseases and their genetics:
Duchenne Muscular Dystrophy
Spinal Muscular Atrophy
Myotonic Muscular Dystrophy
DUCHENNE MUSCULAR
DYSTROPHY
• Duchenne Muscular Dystrophy, also known
as DMD is classified as an X-linked disorder
• The mutation in the DMD gene causes
Duchenne muscular dystrophy
• The DMD gene encodes for the production
of dystrophin, a protein located primarily in
skeletal and cardiac muscle and helps
stabilize and protect muscle fibers
DUCHENNE MUSCULAR
DYSTROPHY
• The female counterpart is a carrier in this
disease, and it is rare for the female to show
symptoms of the disease
• If the female counterpart is a carrier, this
means the disease can be given to a male
offspring if they received the X chromosome
mutation
• If the mother has a daughter, she too can
become a carrier if she receives the X
chromosome mutation.
DUCHENNE MUSCULAR
DYSTROPHY
Symptoms
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· Frequent falls
· Muscle weakness
· Trouble walking
· Trouble running
· Waddling gait
· Big calves
· Difficulty swallowing
· Fatigue
· Possibility of scholiosis
SPINAL MUSCULAR ATROPHY
• Spinal Muscular Atrophy, also known as
SMA is classified as an autosomal recessive
disorder
• This is caused by mutations on
chromosome 5 in a gene called SMN1
• This means, there is a deficiency of a motor
neuron called “SMN” OR “survival of motor
neuron.”
• In this type of situation, both the mother
and father are carriers of this disease
SPINAL MUSCULAR ATROPHY
• There are 4 major types of SMA:
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Type I
Type II
Type III
Type IV
SPINAL MUSCULAR ATROPHY
• Type I
• Usually diagnosed during an infant’s first six months.
• Babies with SMA type I face many physical challenges, including muscle
weakness and trouble breathing, coughing, and swallowing
• They may need breathing assistance or a feeding tube
• Often fatal early on in life
• 60% of all SMA cases are Type I
• Also known as Werdnig-Hoffmann disease.
SPINAL MUSCULAR ATROPHY
• Type II
• Usually diagnosed after six month of age, but before two years of age.
• The first sign is often a delay in meeting motor milestones, or failing to meet
milestones entirely
• Individuals affected by SMA type II can typically sit up without help, though they
may need assistance getting into a seated position, but they are unable to walk
and will require a wheelchair
SPINAL MUSCULAR ATROPHY
• Type III
• Usually diagnosed after 18 months of age, but before three years of age
• However, SMA type III can be diagnosed as late as the teenage years
• Individuals affected by SMA type III are initially able to walk, but have
increasingly limited mobility as they grow and eventually, many need to use a
wheelchair
• Also called Kugelberg-Welander disease or juvenile SMA
SPINAL MUSCULAR ATROPHY
• Type IV
• SMA type IV is very rare
• It usually surfaces in adulthood, and it leads to mild motor impairment
• While symptoms can begin as early as age 18, they usually begin after age 35
SPINAL MUSCULAR ATROPHY
• Most people have two copies of the SMN1 gene
• Individuals who have one faulty copy and one functioning copy are called
carriers
• Carriers do not have SMA, but they may pass the faulty gene on to their
children
• SMA is an autosomal recessive genetic disorder
• This means that, generally, both parents must pass on the mutation for the
child to have SMA
• When two carriers have a child, there is a 25% chance that the child will be
unaffected, a 50 % chance that the child will also be a carrier, and a 25%
chance that the child will have SMA.
MYOTONIC MUSCULAR
DYSTROPHY
• Myotonic Muscular Dystrophy, also known as MMD, is classified as an
autosomal dominant disorder carried on chromosome 19 or 3
• Myotonic dystrophy type 1 is caused by mutations in the DMPK gene, while
type 2 is caused by mutation in the CNBP gene
MYOTONIC MUSCULAR
DYSTROPHY
• These genes' functions are not yet clear, but the protein that is produced
from the DMPK gene affect in type 1 may play a role in intercellular
communications
• The mutated gene produces an expanded form of mRNA which forms
clumps inside the cell and interferes with the production of other proteins,
thus leading to the symptoms of myotonic muscular dystrophy
MYOTONIC MUSCULAR
DYSTROPHY
Symptoms
• Difficulty releasing one’s grip
• Weakness of muscles in the hands and
feet
• Difficulty swallowing
• Abnormal heart rhythms
CONCLUSION
• For each type of neuromuscular disease, there is some type of mutation that
causes a change in the production of some type of protein, directly or
indirectly
• The short term treatment involves the injection of the missing, necessary
proteins for muscular functions
• However, in order to cure the disease, the DNA of the individual's cells must
be altered in some way in order to correct the mutation, or to function in a
way that would compensate for the mutation
• As science and technology continues to progress, it may be possible to
change an individual's DNA without risk factors and completely cure the
disease, however presently, there are other treatments of the diseases that
involve minor DNA translations, corrections, addition of proteins, etc.
FOLLOW UP QUESTIONS
• Can the inherited mutation be repaired after the individual is diagnosed?
• Why are parents not tested for the mutation in order to predict or prevent
the spread of disease?
WORKS CITED
• https://encryptedtbn1.gstatic.com/images?q=tbn:ANd9GcR4vYyGpPcEUkmFifSc8myv9qtq3sWylYfuQr
H2v2J2afTWz5q6
• https://www.mda.org/sites/default/files/publications/Facts_Genetics_P-210_1.pdf
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• http://ghr.nlm.nih.gov/condition/myotonic-dystrophy ws:end:WikiTextUrlRule:420
• http://ghr.nlm.nih.gov/condition/duchenne-and-becker-muscular-dystrophy
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• https://www.mda.org/disease/duchenne-muscular-dystrophy/overview
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• http://www.curesma.org/sma/about-sma/?referrer=https ws:end:WikiTextUrlRule:423
://www.google.com/