Bloom syndrome

In Bloom 's syndrome, which is also known under the term congenital teleangiektatisches syndrome, is a rare, hereditary disease that is classified by the human geneticists in the group of so-called chromosome breakage syndromes.

The passing on of mutations associated with this disease follows an autosomal recessive inheritance. This form of inheritance can also be observed in other chromosomal instability syndromes, such as ataxia telangiectasia ( Louis-Bar syndrome) or Fanconi anemia.

Epidemiology

An exact frequency can be specified only difficult, but we know that it is slightly increased in a specific population group, the Ashkenazi Jews. It is estimated here a frequency of about 1:48.000 and a share of about 0.5 % heterozygous for the mutation blmAsh. It appears, however, due to the recessive inheritance scheme as well as no manifestation in heterozygosity.

Clinic

Affected often fall on by characteristic for this syndrome facial features, further in the literature, the following symptoms and abnormalities are described:

  • Proportioned dwarfism
  • Telangiectasia of the skin
  • Skull deformities
  • High sensitivity to the sun with hyper-or hypopigmentation
  • Increased susceptibility to infections due to different immune defects
  • Increased rate of malignancies (eg, leukemia )

Cause

As the cause of the Bloom syndrome mutations in the BLM gene have been identified, which codes for the Bloom 's syndrome protein, a RecQ 3'-5 ' helicase, an enzyme that monitors the integrity of the interphase of the cell cycle. Mutations in this region lead to errors during replication or repair of DNA. The recombination is influenced in this way. This manifests itself in an increased rate of sister chromatid (abbreviated SCE sister chromatid exchanges for ), which can be visualized using certain techniques. The SCEs represent a kind of " mitotic crossing over" is, therefore, an exchange of chromosomal fragments under the individual sister chromatids. It can be observed simultaneously during mitosis partially through 50 SCE if a Bloom syndrome is present. In comparison, the number for non- sufferers amounted to a maximum of 6 to 10 SCE.

Other features that can be observed, are aberrations that lead to symmetric quadriradialen figures. This can be detected with conventional cytogenetic techniques. However, these are not specific for the Quadriradiale Bloom syndrome. It can be observed among others in the Fanconi anemia.

The occurrence of micronuclei is a phenomenon which is relatively often observed in Bloom 's syndrome. These are small protrusions of the nucleus, which may then assume almost the extent of Kernabschnürung. These lobes can be included in the form of DNA or RNA genetic material.

Genetic diagnosis

The investigation of the characteristic changes in Bloom 's syndrome or other chromosomal instability syndromes are the pre- and postnatal diagnostics accessible. It can capture the above -mentioned characteristics with conventional banding and staining. However, the maximum resolution relates here only 2 to 5 mega basepairs, thus can not directly identify the mutations. Thus, the detectable in conventional cytogenetics changes present only the results from the mutations changes represent a molecular genetic analysis is therefore also particularly important to make an accurate statement about the causal changes.

Therapy

Currently there is no causal treatment strategy. The therapeutic options are limited to a strict medical surveillance to detect which eventually developing malignancies at an early stage. Furthermore, a specific antibiotic prophylaxis and therapy is needed due to the recurrent infections. Also, a special strategy for the development of immunization schedules is necessary because, for example, live vaccines are of limited applicability and active immunization represents a particular risk here.

Autosome Recessive trait Bloom syndrome protein Base pair
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