Transcript Progression

The molecular basis of
muscular dystrophy
(肌营养不良)
Wenya Hou
Xue Jing
Yitang Wang
Jiezhong Zhang
OUTLINE
 INTRODUCTION
 Duchenne
muscular dystrophy (DMD)
 Dysfelin
 Therapeutic Approaches
and perspective
a
quarter of a million kids and
adults are living with the
disease, so chances are you
may know someone who has
it.
What is Muscular Dystrophy?
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The muscular dystrophies (MD) are a group of
more than 30 genetic diseases characterized by
progressive weakness and degeneration of the
skeletal muscles that control movement. Some
forms of MD are seen in infancy or childhood,
while others may not appear until middle age or
later. Muscular dystrophies in general are a group
of genetic, degenerative diseases primarily
affecting voluntary muscles.
 Healthy
muscle
tissue (left).
 Muscular
dystrophy
(right).
HOW TO RECOGNIZE IF MUSCLE WEAKNESS
IS CAUSED BY MUSCULAR DYSTROPHY
 Mostly
affects boys (rarely girls).
 Often brothers or male relatives have same
problem.
 First signs appear around ages 3 to 5: the
child may seem awkward or clumsy, or he
begins to walk 'tiptoe' because he cannot
put his feet flat. Runs strangely. Falls often.
 Problem gets steadily worse over the next
several years.
HOW TO RECOGNIZE IF MUSCLE WEAKNESS IS
CAUSED BY MUSCULAR DYSTROPHY
 Muscle
weakness first affects feet, fronts
of thighs, hips, belly, shoulders, and
elbows. Later, it affects hands, face, and
neck muscles.
 Most children become unable to walk by
age 10.
 May develop a severe curve of the spine.
 Heart and breathing muscles also get
weak. Child usually dies before age 20
from heart failure.
There are probably nine types of
muscular dystrophy.
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Duchenne muscular dystrophy (DMD)
Becker muscular dystrophy (BMD)
Emery-Dreifuss muscular dystrophy (EDMD)
Limb-girdle muscular dystrophy (LGMD)
Facioscapulohumeral muscular dystrophy (FSHD)
Myotonic (pronounced: my-uh-tah-nick) dystrophy (MMD)
Oculopharyngeal Muscular Dystrophy (OPMD)
Distal Muscular Dystrophy (DD)
Congenital muscular dystrophy (CMD)
Duchenne muscular dystrophy
(DMD)
Definition - One of nine types
of muscular dystrophy, a
group of genetic,
degenerative diseases
primarily affecting voluntary
muscles.
 Cause - An absence of
dystrophin, a protein that
helps keep muscle cells
intact.
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DMD
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Onset - Early childhood - about 2 to 6 years.
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Symptoms - Generalized weakness and muscle wasting
first affecting the musclesof the hips, pelvic area, thighs
and shoulders. Calves are often enlarged.
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Progression - DMD eventually affects all voluntary
muscles, and the heart and breathing muscles.
Inheritance - X-linked recessive. DMD primarily affects
boys, who inherit the disease through their mothers.
Women can be carriers of DMD but usually exhibit no
symptoms.
Becker muscular dystrophy (BMD)
 is
similar to DMD but often much less
severe. There can be significant heart
involvement.
Progression - Disease progresses slowly
and with variability. Most with BMD survive
well into mid- to late adulthood.
Emery-Dreifuss muscular
dystrophy (EDMD)
.Cause - Mutations in the genes that produce emerin, lamin A or lamin C,
proteins in the membrane that surrounds the nucleus of each muscle
cell.
 Onset - Usually by 10 years of age.
 Symptoms - Weakness and wasting of shoulder, upper arm and calf
muscles; joint stiffening; fainting (because of cardiac abnormalities).
 Progression - Disease usually progresses slowly. Cardiac
complications are common and sometimes require a pacemaker.
 Inheritance -Can be X-linked recessive, primarily affecting males, who
inherit the disease through their mothers. Another type is autosomal
dominant, meaning it can be inherited through either parent; an
autosomal recessive type occurs when a faulty gene is inherited from
each parent.
Limb-girdle muscular dystrophy
(LGMD)
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Definition - One of nine types of muscular dystrophy, a group of
genetic, degenerative diseases primarily affecting voluntary muscles.
Cause - A mutation in any of at least 15 different genes that affect
proteins necessary for muscle function.
Onset -Childhood to adulthood.
Symptoms - Weakness and wasting first affecting the muscles around
the shoulders and hips (limb girdles).
Progression - Usually progresses slowly, with cardiopulmonary
complications sometimes occurring in later stages of the disease.
Inheritance - Some types are autosomal dominant, meaning LGMD is
inherited from one parent. Other types are autosomal recessive and
occur when a faulty gene is inherited from each parent.
Facioscapulohumeral muscular
dystrophy (FSHD)
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Definition - One of nine types of muscular dystrophy, a
group of genetic, degenerative diseases primarily affecting
voluntary muscles.
Cause - A missing piece of DNA on chromosome 4.
Onset - Usually by age 20.
Symptoms - Weakness and wasting of the muscles
around the eyes and mouth, and of the shoulders, upper
arms and lower legs initially, with later weakness of
abdominal muscles and sometimes hip muscles.
Progression - Progresses slowly with some periods of
rapid deterioration. Disease may span many decad
Myotonic (pronounced: my-uh
-tah-nick)
dystrophy (MMD)
Definition - One of nine types of muscular dystrophy, a group of
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genetic, degenerative diseases primarily affecting voluntary muscles.
Cause - A repeated section of DNA on either chromosome 19 or
chromosome 3.
Onset - Congenital form appears at birth. More common form may
begin in teen or adult years.
Symptoms - Generalized weakness and muscle wasting first
affecting the face, lower legs, forearms, hands and neck, with
delayed relaxation of muscles after contraction common. Other
symptoms involve the gastrointestinal system, vision, heart or
respiration. Learning disabilities occur in some cases. Congenital
myotonic dystrophy is the more severe form.
Progression - Progression is slow, sometimes spanning 50 to 60
years.
Inheritance - Autosomal dominant; the disease may be inherited
through either the father or the mother.
Oculopharyngeal Muscular
Dystrophy
(OPMD)
 Definition - One of nine types of muscular
dystrophy, a group of genetic, degenerative
diseases primarily affecting voluntary muscles.
 Cause - A faulty gene for poly(A)-binding protein
nuclear 1 (PABPN1), which is suspected to lead to
production of extra chemical material that causes
formation of clumps in the muscle cells.
 Onset - Usually not until the 40s or 50s.
 Symptoms - OPMD first causes weakness of the
muscles of the eyelids and throat; weakness of
facial and limb muscles often occurs later.
Swallowing problems and difficulty keeping the
eyes open are common problems.
 Progression - Slow.
Distal Muscular Dystrophy (DD)
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Definition - A class of muscular dystrophies that primarily
affect distal muscles, which are those of the lower arms,
hands, lower legs and feet. Muscular dystrophies in general
are a group of genetic, degenerative diseases primarily
affecting voluntary muscles.
Cause - A mutation in any of at least eight genes that affect
proteins necessary to the function of muscles.
Onset - childhood to adulthood
Symptoms - Weakness and wasting of muscles of the hands,
forearms and lower legs.
Progression - Slow progression; not life-threatening.
Inheritance - May be autosomal dominant, meaning a faulty
gene is inherited from one parent; or autosomal recessive,
occurring when a faulty gene is inherited from each parent.
Congenital muscular dystrophy
(CMD)
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Definition - A class of muscular dystrophies that show themselves at or near
birth. Muscular dystrophies in general are a group of genetic, degenerative
diseases primarily affecting voluntary muscles.
Cause - Genetic mutations affecting some of the proteins necessary for
muscles and sometimes for the eyes and/ or brain.
Onset - At or near birth.
Symptoms - Generalized muscle weakness with possible joint stiffness or
looseness. Depending on the type, CMD may involve spinal curvature,
respiratory insufficiency, mental retardation or learning disabilities, eye
defects or seizures.
Progression - Varies with type; many are slowly progressive; some shorten
life span.
Inheritance - Autosomal recessive or autosomal dominant; these diseases
are sometimes inherited through both parents and sometimes inherited from
one parent . They can also occur spontaneously because of a newly
developed genetic flaw (mutation).
Duchenne muscular dystrophy (DMD)
ERM family
Spectrin
family
e.dystrophin
muscular dystrophy