The Genetics of Bloom’s Syndrome

BSyn is genetically determined, inherited as a rare autosomal recessive trait – both sexes affected; sibs the only affecteds in a given family; parental consanguinity common. The gene mutated, which is named BLM, is located in band q26.1 on chromosome No. 15.

Chromosome 15.

Bloom’s Syndrome-Causing Mutations Identified in Persons in the Bloom’s Syndrome Registry*

(click to enlarge)

Examples of Cellular Effects of Bsyn-Causing Mutations Observable Microscopically by Immunofluorecence Employing Anti-Blm Protein Antibody Tagged with Rhodamine or Fluorescein*

Control. The color, therefore the BLM protein, is nuclear, some distributed throughout the nucleus, some concentrated in punctuate foci.

Cultured fibroblasts from a person of normal height, and lacking mutation of gene BLM (image to the left), and from two persons with Bloom's syndrome (images below). The lower left image (rhodamine) shows cultured cells from a person with Bloom's syndrome who is homozygous for blmAsh , a mutation that results in a STOP codon, and therefore a polypeptide (or protein) necessarily lacking BLM's nuclear localization signal.(NLS). The lower right image (fluorescein) shows cultured cells from a person with Bloom's syndrome who has two different Bloom's syndrome-causing mutations, one truncating as depicted in the graphic representation of the gene BLM above, the other a missense mutation in the DNA helicase region of BLM (also depicted in the same graphic above), therefore, encoding the mRNA for a BLM protein that is non-functional with respect to DNA helicase activity.

Bloom’s syndrome. The nuclei are “black holes, ” there being a total absence of nuclear fluorescence, therefore of BLM protein. The cytoplasmic fluorescence is of unknown significance.
Bloom’s syndrome. Diffuse fluorescence plus foci, therefore resembling the control’s pattern.

* Sanz et al, 2000

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