DNA Carrier Testing for Genetic Diseases
The following information describes carrier testing
for recessive genes. Some people desire this kind of information
to assist their planning for children. You may or may not. The
information is probably not related to the reasons that you are
having prenatal diagnosis. Also, the information may be confusing
or distracing or anxiety producing. We want you to have access
to carrier testing if you wish to consider it. However, we do
not want you to feel pressured if the testing would not be useful
to you.
Carrier testing for recessive genes applies to relatively uncommon
disorders. People who are carriers of recessive genes are not
ill, but under some circumstances, could have a child with a disease
state.
Carrier testing is entirely voluntary.
The tests are simple blood tests. They may be covered by health
insurance but often are not. There is some concern that being
identified as a carrier of a recessive gene might cause difficulty
in getting or maintaining health insurance, although this type
of discrimination does not appear to be widespread.
Everyone carries a few abnormal "hidden"
or recessive genes. These abnormal recessiv e genes are passed
from generation to generation, usually without causing any problems.
However, if both the mother
and the father happen to have the same
abnormal recessive gene, they could
have a child with a recessive disease.
When both parents carry
one copy
of the same recessive gene,
the parents are said to be at high risk of having children with
the disease. With such a high risk couple, there is a one in four
chance in each pregnancy that
a child will inherit two copies of the gene and be affected by the disease.
Even in such a high risk couple, there is a three in four chance
in each pregnancy
of having a child without the disease.
DNA carrier screening can find most couples
of north European ancestry or European Jewish ancestry who are
at high risk (one in four chance) for having children with cystic
fibrosis. In addition, it can find most couples of Ashkenazi (east
European) Jewish ancestry who are at high risk of having children
with Tay-Sachs disease, Canavan disease, Niemann-Pick disease,
Niemann-Pick disease type A, Fanconi anemia Group C and Gaucher
disease. Carrier screening can also find almost all couples of
African, Mediterranean, Hispanic, Asian and Middle Eastern ancestry
who are at high risk for having children with a serious inherited
anemia.
Fragile X syndrome is the second most common genetic cause of mental
retardation, after Down syndrome, and occurs among people of all
ethnic backgrounds. A gene which is sex-linked is resopnsible
for causing fragile X syndrome and virtually all women who carry
that gene can be found. Only women who carry an abnormal fragile
X gene are at risk of having children with the disorder. Boys
with Fragile X syndrome have moderate to severe mental retardation.
In girls who have the fragile X gene, about half show borderline
to mild retardation and the other half have normal intelligence.
If both
members of a couple are found to carry
the same
recessive gene for one of the following diseases, or if a woman
is found to carry an abnormal fragile X gene, then highly accurate
prenatal diagnosis of the disease is possible. This is done by
chorionic villus sampling (CVS) beginning at 10 weeks of pregnancy
or by amniocentesis beginning at 15 weeks.
If you have carrier testing at the same
time as a CVS or amniocentesis, cells from your CVS or amniocentesis
can be saved pending the results of your tests. Should your pregnancy
be discovered to be at high risk, further testing can usually
be performed on these cells. At times, however, there are not
enough cells from your amniocentesis or CVS and, in that instance,
a procedure would have to be performed again to carry out the
diagnosis.
The following are two genetic
disorders for which carrier testing is available for ALL INDIVIDUALS:
Cystic Fibrosis and Fragile
X:
Disorder -Cystic Fibrosis
Symptoms - Thick secretions lead to chronic
lung disease, gastrointestinal tract problems with malnutrition.
Sterility in men. Normal intelligence.
Prognosis - Highly variable; average life
span is now over 30 years. Severe disease can lead to death during
childhood; mild disease is compatible with survival into later
adulthood.
Carrier Frequency and Disease Incidence
-
1/25 whites (Jews and non-Jews) carry gene;
risk of affected child: 1/2500
1/80 African Americans carries gene; risk of affected child 1/25,000
Genetic Testing for Carrier Status-
DNA tests detect 97% of European Jewish
gene carriers, 90% of northern European non-Jewish gene carriers;
70% or less of carriers from other ethnic groups
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Disorder - Fragile X syndrome
Symptoms - Moderate to severe mental retardation
in males; autistic-like behavior may be present; 60% of females
with borderline to mild retardation; 40% of females have intelligence
in the normal range without recognized symptoms of the disorder.
Prognosis - Moderate to severe retardation
may be recognizable during early childhood; less severe presentation
may not be obvious until school age.
Carrier Frequency - 1/400 women (of any
ethnic background) carries fragile X premutation (abnormal gene
predisposing to having children with fragile X syndrome).
Disease Incidence - 1/1200 males affected
1/2000 females affected
Genetic testing for carrier status - DNA
test detects virtually all carriers of the common fragile X mutation
For a child to be affected by cystic fibrosis,
BOTH parents must be gene carriers. For fragile X syndrome, only
the mother must be
a carrier. A negative (normal) DNA test reduces greatly, but does
not eliminate, risk of being a carrier. Carrier frequencies stated
above refer to individuals without a family history of the disorder
Recessive gene carrier testing options
for individuals of Central/Eastern European (Ashkenazi )Jewish
ancestry):
Disorder - Tay-Sachs disease
Symptoms - Brain cells die leading progressively
to severe retardation, seizures, and blindness starting at 4-6
months of age.
Prognosis - Death usually occurs by age
6 years. No effective treatment is currently available.
Carrier Frequency and Disease Incidence
- ~1/30 Jews carries gene; risk of affected child: 1/3600
~1/300 non-Jews carries gene
Genetic Testing for Carrier Status - DNA
tests detect 94% of Jewish gene carriers. Enzyme testing will
detect almost all carriers of common Tay-Sachs mutations.
Disorder - Canavan Disease
Symptoms - Similar to Tay-Sachs disease.
Prognosis - Death usually occurs by age
10 years although survival into adulthood occasionally occurs.
No effective treatment is currently available.
Carrier Frequency and Disease Incidence
- ~1/40 Jews carries gene; risk of affected child: 1/6400
~1/500 non-Jews in U.S. carries gene
Genetic testing for carrier status - DNA
tests detect 98% of Jewish gene carriers. Carrier testing in other
ethnic groups is less accurate.
Disorder
- Niemann-Pick disease, Type A
Symptoms - Severe feeding problems and
failure to grow with progressive and severe degeneration of brain
function in early infancy.
Prognosis - Death usually occurs by age
3. No effective treatment is currently available.
Carrier Frequency and Disease Incidence
- ~1/90 Jews carries gene; risk of an affected child: 1/32,000;
~1/300 among non-Jews
Genetic testing for carrier status - DNA
tests will detect 95% of Jewish gene carriers. Carrier testing
in other ethnic groups is less accurate.
Disorder
- Fanconi anemia, Group C
Symptoms- Bone marrow failure, malformations
of heart, kidney, limbs; 10-15% risk of leukemia
Prognosis - Death usually occurs in first
or second decade; occasional longer term survivors; treatment
by transfusions, drugs, bone marrow transplant
Carrier Frequency and Disease Incidence-
~1 in 90 Jews carries gene; risk of an affected child: 1/32,000
Genetic testing for carrier status - DNA
test will detect virtually all Jewish carriers. Carrier testing
in other ethnic groups is less accurate
Disorder - Gaucher disease
Symptoms - Anemia, bone pain, enlargement
of spleen and liver; normal intelligence; rarely nervous system
is involved.
Prognosis - Disease is usually mild and
often not diagnosed until adulthood (and sometimes never). Some
suffer from chronic disability, starting in childhood or early
adulthood. Enzyme treatment available for severe symptoms.
Carrier Frequency and Disease Incidence-~1/15
Jews carries gene,~1/200 non-Jews carries gene
1/900 Jews is affected.
Genetic testing for carrier status - DNA
tests detect 95% of Jewish carriers.
Disorder - Bloom syndrome
Symptoms - Growth deficiency, immunodeficiency
and predisposition to cancer
Prognosis - Affected individuals usually die of cancer by age
30. Intelligence is normal.
Carrier Frequency and Disease Incidence-1/100
Jews carries gene, very rare among non-Jews
1/40,000 Jews is affected
Genetic testing for carrier status - DNA
tests detect 97% of Jewish carriers.
For a child to be affected by Tay-Sachs
disease, Canavan, Niemann-Pick Type A, Fanconi anemia Group C,
Gaucher disease disease BOTH parents must be gene carriers.
A negative (normal) DNA test reduces greatly, but does not eliminate,
risk of being a carrier. Carrier frequencies above refer to individuals
without a family history of the disorder.
Recessive gene carrier testing options
for individuals of African, Hispanic, Mediterranean, Asian and
Middle Eastern ancestry:
Disorder - Sickle Cell disease
Symptoms - Severe anemia, bone pain, damage
to major organs, susceptibility to infection, normal intelligence
Prognosis - highly variable; severe disease
can lead to frequent hospitalizations; mild disease is compatible
with survival to adulthood; Treatment: drugs; transfusions
Carrier Frequency Disease Incidence - 1/11
African Americans carries gene; risk of affected child: 1/484
less than 1/50 individuals of Mediterranean, Arabian, Asian Indian
ancestry carry gene
Genetic Testing for Carrier Status - Hemoglobin
electrophoresis finds all carriers of sickle cell gene.
Disorder - Thalassemia
Symptoms - Severe anemia, transfusion dependency, organ damage,
normal intelligence
Prognosis - variable; depends on specific
mutations in family; in severe cases, complications of disease
and treatment lead to death during third and fourth decades. Treatment:
transfusions, drugs, bone marrow transplantation.
Carrier Frequency Disease Incidence - about
1 in 20 individuals with Mediterranean or Indian ancestry carry
gene. Risk of affected child: about 1 in 1600. 1 in 75 African
Americans carries gene .1 in /10 Southeast Asians carries gene
Genetic testing for carrier status - Hemoglobin
electrophoresis and complete blood count will find almost all
carriers of common inherited anemias.
For a child to be affected by sickle cell
or disease or thalassemia, BOTH parents must be gene carriers.
Carrier testing will find all carriers of sickle cell disease
and almost all carriers of thalassemia. Carrier frequencies above
refer to individuals without a family history of the disorder.
information provided courtesy of:
DNA Carrier Testing for Genetic
Diseases
Department of Genetics
Yale University School of Medicine
(203) 785-2661
Obstetrics-Gynecology-Infertility Group, PC
203-562-5181