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Bloom syndrome
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Types and clinical signs
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This is a severe disease that causes delayed growth in infancy, very short stature
in later life, a characteristic facial appearance, sensitivity to sunlight that
causes a characteristic rash on the face, and a tendency to develop cancerous tumors
at a young age. All these result from the defective production of a protein whose
function is to repair the damage that occurs spontaneously in DNA.
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Inheritance pattern
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Autosomal
recessive.
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Penetrance
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Full
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Associated features that can be demonstrated in tests performed during pregnancy
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There are no specific ultrasound signs and no associated defects.
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What is the risk of recurrence in a subsequent pregnancy?
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For a couple who has already had an affected child, the risk is 25% in every subsequent
pregnancy. This also applies to a couple where both partners have been found to
carry mutations for Bloom syndrome.
When only one parent carries the abnormal gene, there is no risk that any of their
offspring will have the disease; however, in such families there is a 50% chance
that the infant will be a carrier, but he himself will be healthy, like the carrier
parent.
The risk for more distant relatives depends on the degree of relationship between
the relatives and the affected individuals, the ethnic groups of their partners,
the presence of family members with Bloom syndrome in the partners' families, consanguinity between the
parents, if present, etc. and is established within genetic counseling.
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Molecular genetic information
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The gene for the disease
The gene, BLM, is responsible for producing the protein DNA helicase RevQ protein-like-2.
Location
The long arm of chromosome 15 - 15q26.
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Genetic testing
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Diagnostic testing
A direct test can be performed to identify the mutation in the gene by testing for
the common mutations. See: Testing the disease-causing
gene for mutations that are common in a specific ethnic group - autosomal recessive
diseases.
Carrier testing
The disease is common in Ashkenazi Jews. The carrier frequency in the healthy Ashkenazi
Jewish population is approximately 1:100. Unlike
cystic fibrosis, where there are a number of mutations in the gene that
causes the disease, in Bloom syndrome, only one mutation common to all affected
individuals and carriers has been found in the Ashkenazi Jewish population. In Jews
of other ethnic groups, carriers cannot be identified. It is therefore advisable
to perform the test in couples when one of the partners is of full or partial Ashkenazi
origin.
Carrier status testing in relatives of patients with Bloom syndrome
It is important that relatives of patients with Bloom syndrome clarify which mutations
are present in the patient or parents in their family in order to ascertain that
they are included in the battery of mutations routinely tested for - otherwise it
will be necessary to expand the list of mutations tested for and/or examine the
partner. This will be discussed in genetic counseling. See also: Introduction to cystic fibrosis, Gaucher disease, Canavan
disease, familial dysautonomia, Bloom syndrome and Fanconi anemia.
Fetal testing
Same as the diagnostic test.
Prenatal diagnosis (amniocentesis)
can also be offered to each couple who has had an affected child. The best way is
after identifying the mutations in the parents, but if these are not found, indirect
linkage analysis can be performed. See: Indirect testing for genetic
markers in a family that has one or more patients - when there is only one gene
that can cause the disease - autosomal recessive diseases.
Preimplantation diagnosis (before the embryonic cells implant in the uterine wall)
can also be offered for this disease - this is performed in special centers, mainly
overseas, and in special cases this can be considered within genetic counseling.
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