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UNSW
Embryology
DNA- NCBI Genes and
Diseases
Muscle
Introduction
Duchenne
Muscular Dystrophy
Ellis-Van Creveld Syndrome
Marfan
Syndrome
Myotonic
Dystrophy
About Notes
Nervous
Muscle
Immune
Metabolism
Signals
Transport
Introduction
Link to NCBI page
DUCHENNE MUSCULAR DYSTROPHY (DMD) is one of a group of
muscular dystrophies characterized by the enlargement of
muscles. DMD is one of the most prevalent types of muscular
dystrophy and is characterized by rapid progression of
muscle degeneration which occurs early in life. All are
X-linked and affect mainly males - an estimated 3,500 boys
worldwide.
The gene for DMD, found on the X chromosome,
encodes a large protein - dystrophin. Dystrophin is required
inside muscle cells for structural support: it is thought to
strengthen muscle cells by anchoring elements of the
internal cytoskeleton to the surface membrane. Without it,
the cell membrane becomes permeable, so that extracellular
components enter the cell, increasing the internal pressure
until the muscle cell 'explodes' and dies. The subsequent
immune response can add to the damage.
A mouse model for DMD exists, and is proving
useful for furthering our understanding on both the normal
function of dystrophin and the pathology of the disease. In
particular, initial experiments that increase the production
of utrophin, a dystrophin relative, in order to compensate
for the loss of dystrophin in the mouse are promising, and
may lead to the development of effective therapies for this
devastating disease.
Link to NCBI page
ELLIS-VAN CREVELD syndrome, also known as
'chondroectodermal dysplasia', is a rare genetic disorder
characterized by short-limb dwarfism, polydactyly
(additional fingers or toes), malformation of the bones of
the wrist, dystrophy of the fingernails, partial hare-lip,
cardiac malformation and often prenatal eruption of the
teeth.
The gene causing Ellis-van Creveld syndrome,
EVC, has been mapped to the short arm of chromosome 4. As
yet, the function of a healthy EVC gene is not known; this
is one of the most important questions that must be answered
about the disease, since it would give an indication as to
the molecular mechanism of the disease.
Ellis-van Creveld syndrome is often seen among
the Old Order Amish community in Lancaster County,
Pennsylvania. Because this group of people is small and
isolated, it affords a rare opportunity to observe the
passage of this particular disorder from generation to
generation. A pattern of inheritance can be observed that
has indicated the disease is autosomal-recessive (i.e. a
mutated gene form both parents is required before the
effects of the disease to become apparent).
Link to NCBI page
MARFAN SYNDROME is a connective tissue disorder, so
affects many structures, including the skeleton, lungs,
eyes, heart and blood vessels. The disease is characterized
by unusually long limbs, and is believed to have affected
Abraham Lincoln.
Marfan syndrome is an autosomal dominant
disorder that has been linked to the FBN1 gene on chromosome
15. FBN1 encodes a protein called fibrillin, which is
essential for the formation of elastic fibres found in
connective tissue. Without the structural support provided
by fibrillin, many tissues are weakened, which can have
severe consequences, for example, ruptures in the walls of
major arteries.
Beta blockers have been used to control some of
the cardiovascular symptoms of Marfan syndrome; however,
they are not effective against the skeletal and ocular
problems, which can also be serious. A related disease has
been found in mice, and it is hoped that the study of mouse
fibrillin synthesis and secretion, and connective tissue
formation, will further our understanding Marfan syndrome in
humans.
Link to NCBI page
MYOTONIC DYSTROPHY is an inherited disorder in which the
muscles contract but have decreasing power to relax. With
this condition, the muscles also become weak and waste away.
Myotonic dystrophy can cause mental deficiency, hair loss
and cataracts. Onset of this rare disorder commonly occurs
during young adulthood. However, it can occur at any age and
is extremely variable in degree of severity.
The myotonic dystrophy gene, found on chromosome
19, codes for a protein kinase that is found in skeletal
muscle, where it likely plays a regulatory role.
An unusual feature of this illness is that its
symptoms usually become more severe with each successive
generation. This is because mistakes in the faithful copying
of the gene from one generation to the next result in the
amplification of a 'AGC triplet repeat', similar to that
found in Huntington disease. Unaffected individuals have
between 5 and 27 copies of AGC, myotonic dystrophy patients
who are minimally affected have at least 50 repeats, while
more severely affected patients have an expansion of up to
several kilobase pairs.
Link to NCBI page
About Notes
These notes are derived from the NCBI WWW pages Genes and Disease. They are included here for computers without internet access and for educational purposes only. Where possible use the WWW link at the bottom of each section to see the original pages which include images and many Links to other resources.