Chromosome Analysis, Sister Chromatid Exchange (SCE) for Bloom Syndrome, Blood
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Bloom syndrome is a genetic disorder associated with various congenital defects and predisposition to acute leukemia, pulmonary fibrosis, and Hodgkin lymphomas. Carcinoma also is commonly seen in these patients. Approximately one fourth to one half of patients develop some type of cancer with a mean age of 25 years at onset. The severity and age of onset of cancer varies among patients.
These patients often have prenatal or postnatal growth retardation, short stature, malar hypoplasia, telangiectatic erythema of the face and other regions, hypo- and hyperpigmentation, immune deficiencies, occasional mild mental retardation, infertility, and high-pitched voices.
Bloom syndrome is an autosomal recessive disorder caused by mutations in the BLM gene located at 15q26.1. While multiple mutations have been detected, the use of molecular testing to diagnose Bloom syndrome is limited in many ethnic groups. Patients with Bloom syndrome demonstrate a high frequency of chromosome abnormalities when their cells are cultured. Thus, cytogenetic studies can be helpful to establish a diagnosis.
Bloom syndrome results in 2 characteristic cytogenetic abnormalities. First, the cells are at increased risk for random breaks leading to fragments or exchanges between nonhomologous chromosomes. Second, cells in these patients have an increased frequency of sister chromatid exchanges (SCE: exchange of material between homologous chromosomes) of approximately 10-fold to 20-fold higher than average.
This test is diagnostic for Bloom syndrome. Carrier testing for Bloom syndrome is performed by different methodologies, so this test should not be ordered for that purpose.
As a diagnostic test for Bloom syndrome
The observation of a 10-fold or more increase in spontaneous sister chromatid exchange (SCE) relative to a control specimen and historical reference values is a diagnostic cytogenetic finding for Bloom syndrome.
Spontaneous SCE that is more than 10 times greater than the normal control could indicate exposure to a toxic substance. Therefore, clinical correlation is required.
A normal result does not rule out the possibility of birth defects, such as those caused by chromosomal abnormalities, molecular mutations, and environmental factors (ie, teratogen exposure). The test does not rule out other numeric or structural abnormalities. If a constitutional chromosome abnormality is suspected, a separate conventional cytogenetic study, CMS / Chromosome Analysis, for Congenital Disorders, Blood should be requested.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test cannot be used to identify heterozygote carriers for Bloom syndrome and is not appropriate as part of a prenatal screening panel.
-Cell lysis caused by forcing the blood quickly through the needle
-Use of an improper anticoagulant (sodium heparin is best) or improperly mixing the blood with the anticoagulant
-Excessive transport time
-Inadequate amount of blood (we recommend 5 mL for adults and 2-5 mL for children)
-Exposure of the specimen to temperature extremes
-T lymphocytes that do not respond to mitogens used to stimulate T cells to undergo mitosis (rare)
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Dicken CH, Dewald G, Gordon H: Sister chromatid exchanges in Bloom's syndrome. Arch Dermatol 1978:114;755-760
2. Kato H: Spontaneous sister chromatid exchanges detected by BUdR-labelling method. Nature 1974:251;70-72
3. Korenberg JR, Freedlender EF: Giemsa technique for the detection of sister chromatid exchanges. Chromosoma 1974:48;355-360
4. Latt SA: Microflurometric analysis of deoxyribonucleic acid replication kinetics and sister chromatid exchanges in human chromosomes. J Histochem Cytochem 1974:22;478-491
5. Perry P, Wolff S: New Giemsa method for the differential staining of sister chromatids. Nature 1974:251;156-158