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Reciprocal Translocation ( between the arms of any two chromosomes )
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What is a chromosome disorder and what is its significance?
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Chromosomes are the structures
in which our hereditary material (DNA) is packed.
A healthy person has 46 chromosomes (23 pairs). One chromosome of each pair (i.e.
a total of 23 chromosomes) is donated by each parent to the fetus. Twenty-two pairs
are called autosomes, and the 23rd pair consists of the sex chromosomes (X and Y).
Females have two X chromosomes and males have one X and one Y. The chromosome pairs
are arranged and numbered by size and shape, and each has different genes. Because
there are two copies of each chromosome, there is effectively a duplicate gene system
(one maternal and the other paternal), each identical in sequence to the other.
A change in the number or structure of the chromosomes in pairs 1-- 22, causing
an addition or deletion of chromosomal information in these pairs compared with
the normal state, constitutes a significant medical problem. In the great majority
of cases, this change is expressed as severe structural or functional defects in
the tissues and/or mental retardation. For example, an extra number
21 chromosome, resulting in three instead of the normal two so that there are 47
chromosomes altogether, causes Down
syndrome. An extra number 18 chromosome, which is larger and therefore contains
more genes, manifests as a more severe disorder called trisomy 18. In this syndrome, there are severe defects,
and it usually ends in death soon after birth or even in the uterus. This is also
the case with a deletion of the whole or a part, however small, of chromosome 18.
Conversely, the clinical manifestation of a change in the number of sex chromosomes
(X or Y) or their structure is usually less severe. See under "chromosomes".
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What is a translocation?
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This is the exchange of chromosomal material between two chromosomes of different
pairs.
A translocation is said to be balanced when a change occurs in the location of certain
genes, but there is no gain or loss of genetic material.
If a person carries a balanced translocation, with no change in the amount of genetic
material and no damage to the genes has occurred, he will be healthy.
A parent carrying a balanced translocation can have healthy children without a translocation,
or healthy children carrying a balanced translocation like that of the parent.
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In these cases, where the chromosome arrangement is identical to that of the affected
parent, there are no clinical manifestations. The probability that a parent who
carries a balanced translocation will have healthy children is approximately 85%
per pregnancy. However, such a parent does have an increased risk (approximately
15%) of having a child with an unbalanced chromosome arrangement. In such a child,
the chromosome arrangement will include gains or losses of genetic material that
result from the parental translocation. Some fetuses that have an unbalanced chromosome
arrangement abort spontaneously at the beginning of pregnancy, so that some of the
couples where one partner carries a balanced translocation have recurrent miscarriages.
This can be diagnosed during pregnancy by amniocentesis or chorionic villus sampling.
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There are two main types of translocations:
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- Reciprocal translocation - described below. An
inversion is also effectively a translocation of this type.
- Robertsonian
translocation - see corresponding information sheet.
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Reciprocal translocation (and/or inversion)
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This is a condition in which there is an exchange of chromosomal material between
two chromosomes of different pairs. In this condition, there is breaking and rejoining
of two arms of two different chromosomes (reciprocal translocation) or two arms
of the same chromosome (inversion). When the break occurs between the genes and
the genes are not damaged, there are no clinical consequences. However, when as
a result of such a translocation, damage is caused to an essential gene, a mutation
that can cause impaired functioning may arise.
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The significance depends firstly on whether or not one of the parents carries the
same translocation (or inversion) - it is unlikely that both have it.
If one of the parents does carry the translocation, it may also be present in other
family members.
In most cases, one of the parents carries a similar translocation.
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If one of the parents carries such a translocation (or inversion)
If the parent carrying the translocation is completely healthy, it can be expected
that the fetus will also be healthy, without genetic problems arising from the translocation.
If neither parent is a carrier of such a translocation (or inversion)
The chance of finding such a translocation in the fetus on performing amniocentesis
in pregnancies of couples where neither is a carrier of this translocation is 1
in 2,000. If the translocation is not present in either parent, this is described
as a de novo translocation in the fetus, and in this situation the risk for defects
or developmental problems and mental retardation in the baby is 6% - 7%. The defects
are diverse and some can be detected by ultrasound. Therefore, if defects are not
detected by ultrasound, the likelihood that there will be problems in the newborn
is lower (see below). Conversely, if defects or growth retardation are found on
ultrasound examination,
the risk that the child will be mentally retarded is significantly increased. In
genetic counseling,
the risk can be assessed based on the ultrasound findings.
The most common inversions usually occur in chromosomes 2 and 9 and do not involve
a significantly increased risk for defects or mental retardation. These inversions
are usually present in one of the parents too. When a fetus carries an inversion,
the chance that this is present in both parents is very low; 1 out of 10,000 amniocenteses.
In these cases, the inversions are usually not in the common chromosomes.
Are cases of de novo translocation (or inversion) associated with an increased risk
for mental retardation if the ultrasound scan is normal?
Based on a number of reports in which a total of approximately 150 cases were studied,
half of the fetuses carrying translocations had only mental retardation and no defects.
It thus appears that the absence of defects demonstrated by ultrasound is associated
with a greater chance that the fetus will be healthy, but there is still at least
a 3% - 4% risk for mental retardation (twice the normal risk).
It should be mentioned that to date not enough studies have been carried out that
have monitored enough children with de novo translocations detected in pregnancy
for long enough to draw conclusions on their development.
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