Transcript achondroplasia

Genetics
Yu Lu
Department of Rheumatology
Ren Ji Hospital
Achondroplasia
Achondroplasia vs. Chondroplasia
(软骨发育不全) （软骨生成）
achondroPlasia
What is achondroplasia?
• Achondroplasia is a genetic disorder of bone growth that is
evident at birth. It affects about one in every 25,000 births
and it occurs in all races and in both sexes. Its depiction in
ancient Egyptian art makes it one of the oldest recorded birth
defects.
• The word achondroplasia is derived from Greek and means
"without cartilage formation," although individuals with
achondroplasia do have cartilage. During fetal development
and childhood, cartilage normally develops into bone, except
in a few places, such as the nose and ears. In individuals
with achondroplasia, something goes wrong during this
process, especially in the long bones (such as those of the
upper arms and thighs). The rate at which cartilage cells in
the growth plates of the long bones turn into bone is slow,
leading to short bones and reduced height.
What does a person with
achondroplasia look like?
•
A child with achondroplasia has a relatively
normal torso and short arms and legs. The
upper arms and thighs are more shortened than
the forearms and lower legs. Generally, the
head is large, the forehead is prominent and the
nose is flat at the bridge. Sometimes, the large
head size reflects hydrocephalus (excess fluid in
the brain), and require surgery.
• Hands are short with stubby fingers. There is a
separation between the middle and ring fingers
(trident hand). Most individuals with
achondroplasia eventually reach an adult height
of about 4 feet.
What causes achondroplasia?(1)
• Achondroplasia is caused by an abnormal gene located on one
of the chromosome 4 pair (humans have 23 pairs of
chromosomes).
• In some cases, a child inherits achondroplasia from a parent
who also has the condition. If one parent has the condition and
the other does not, there is a 50 percent chance that their child
will be affected. If both parents have achondroplasia, there is a
50 percent chance that the child will inherit the condition, a 25
percent chance that the child will not have it, and a 25 percent
chance that the child will inherit one abnormal gene from each
parent and have severe skeletal abnormalities that lead to early
death. A child who does not inherit the gene will be completely
free of the condition, and cannot pass it on to his or her own
children.
What causes achondroplasia?(2)
• In more than 80 percent of cases, however, achondroplasia is
not inherited but results from a new mutation (change) that
occurred in the egg or sperm cell that formed the embryo. The
parents of children with achondroplasia resulting from new
mutations are usually normal-sized.
Typically, these parents have no other children with
achondroplasia, and the chances of their having a second
affected child are extremely small. Geneticists have observed
that older-than-average fathers (age 40 and older) are more
likely to have children with achondroplasia and certain other
autosomal dominant conditions caused by new mutations.
Individuals with achondroplasia resulting from new mutations
transmit the disorder to their children as described above.
Can achondroplasia be
diagnosed before birth?
• In 1994, researchers identified the gene that causes
achondroplasia. This discovery allowed the
development of highly accurate prenatal tests that
can diagnose or rule out achondroplasia. These tests
can be offered when both expectant parents have
achondroplasia. In such cases, the baby has a onein-four chance of inheriting an abnormal gene from
each parent and developing a fatal form of
achondroplasia. After birth, it generally is diagnosed
by physical examination and X-rays.
How is achondroplasia treated?
• There currently is no way to normalize
skeletal development of children with the
disorder……
Can achondroplasia be
prevented?
• There is no way to prevent the majority of
cases of achondroplasia, since these
births result from totally unexpected gene
mutations in unaffected parents. Genetic
counseling can help affected adults make
informed decisions about family planning.
What research is being done on
achondroplasia?
•
As noted above, scientists have identified the gene, and the exact mutation
(change) in the gene, that causes achondroplasia. The gene is one of a
family of genes that makes proteins called fibroblast growth factor receptors.
Scientists have recently linked these genes with several skeletal disorders.
The fibroblast growth factor receptor gene dictates the production of a
protein that is located on the surface of cells of different tissue types,
including cartilage. The protein normally responds to signals from chemicals
called growth factors which stimulate cell growth and maturation.
Now scientists are investigating how the faulty protein actually causes the
features of achondroplasia. This eventually may lead to improved treatment
for this disorder, as well as improved understanding and treatment of other
skeletal disorders caused by this family of genes. March of Dimes scientists
and other researchers also are working to identify the genes that cause
some of the other more than 100 forms of disproportionate short structure.
•
Additional Sources of
Information
For further information on support groups for individuals with
achondroplasia or other forms of growth deficiency, contact:
Little People of America (LPA)
P.O. Box 745
Lubbock, TX 79408
888-LPA-2001
Human Growth Foundation
997 Glen Cove Ave.
Glen Head, NY 11545
800-451-6434
The Magic Foundation for Children's Growth and Related Adult Disorders
1327 N. Harlem Ave.
Oak Park, IL 60302
708-383-0808
Twins
Twin Operation!
“WOW! Two Iranian Siamese Twins are to be
seprataed!
They are Iranian, and the word Siamese is not an
ethnical modifier of the Twins, but a description of
the fact that they are connected at the head!
Jenna and Barbara
sure are lucky they were not stapled together in the
womb: the surgery will last 48 hours for these
Iranian women: may the operation go smoothly. ”
9/11/2001
• Jenna and Barbara
were wisked away to a
secret location since
September 11th. The
Secret service quickly
protected them due to
the bombing of the
World Trade Center
and The Pentagon.
TheFirstTwins.com is
saddened by the
destruction on
9/11/2001.
Who is Who?

Jenna is on the
left, Barbara is
on the right.
 Barbara is on
the left, Jenna is
on the right.
 Holy body
snatchers,
those ain't them!
Discovery of the Double Helix
• Scientists from several laboratories quickly realized
that unraveling the three dimensional structure of
DNA was the key to understanding its function.
• Using wire models, chemical knowledge, and X-ray
crystallography,
Watson and Crick
established the Double Helix structure of DNA. Two
antiparallel sugar phosphate chains wind around the
outside of the molecule; the nitrogenous bases
project into the interior, where they hydrogen-bond in
pairs, A with T and G with C.
DNA replication
•
Meselson and Stahl demonstrated that
DNA replication is semiconservative,
confirming Watson and Crick's hunch
that the parent molecule unwinds and
each strand then serves as a template
for the synthesis of a new halfmolecule according to base-pairing
rules.
•
Some impressive complexities
underlie the apparent simplicity of
DNA replication, with more than a
dozen extremely rapid and amazingly
accurate process.
（underlie/underline/underlay）
•
After binding of specific proteins, the
initiation of replication begins at
special sites called origins of
replication, forming Y-shaped
replication forks……
DNA repair
• DNA molecules require continuous
monitoring and repair because of ongoing
assault by mutagens
• DNA repair enzymes restore the integrity
of the molecule by processes such as
excision repair, which take advantage of
base paring principles.
Alternative forms of DNA
Polymerase Chain Reaction (PCR)
• Polymerase chain reaction
(PCR), is a common method of
creating copies of specific
fragments of DNA. PCR
rapidly amplifies a single DNA
molecule into many billions of
molecules.
• In one application of the
technology, small samples of
DNA, such as those found in a
strand of hair at a crime scene,
can produce sufficient copies
to carry out forensic tests.