The Principles of Clinical Cytogenetics - Extra Materials - Springer

356 Xiao-Xiang Zhang
Fig. 5. G-Banded and C-banded (inset) image of cells from a patient with Robert syndrome, demonstrating
premature centromere separation (arrows). (Courtesy of Dr. Mazin Qumsiyeh.)
the pathways of DNA repair, recombination, transcription, and replication. Loss of WSN function
could promote genetic instability and disease via recombination-initiated mitotic arrest, cell death, or
gene rearrangement. Mutations have been identified in the WRN gene in all WS-affected individuals
studied, and these mutations were located at different sites across the coding region. All WRN mutations
found to date either create stop codons or cause frame shifts that lead to premature termination.
Not a single missense mutation had been identified. WS is the result of complete loss of function of
the WRN gene product. One splice-junction mutation is found in 50–60% of Japanese WS patients
(50). No genotype–phenotype correlation has been observed.
Bloom Syndrome
Bloom syndrome (BS) is a rare genetic disorder characterized clinically by growth retardation,
proportionately short stature, sun sensitivity, erythematous facial skin lesions, immunodeficiency,
and increased predisposition to cancer. Although BS occurs in many ethnic groups, Ashkenazi Jews
have a significantly higher incidence. The gene frequency in this population is estimated to be 1/110.
Genomic instability is manifested by formations of quadriradial configurations of symmetric shape
with centromeres in opposite arms. This rearrangement occurs before mitosis and is a consequence of
an equal exchange of chromatid segments near the centromeres of two homologous chromosomes.
The most characteristic and consistent cytogenetic feature of BS is the greatly elevated (approximately
10-fold) level of sister chromatid exchange (SCE) in various cell types, such as lymphocytes,