This test analyzes the BLM gene, associated with Bloom syndrome. This rare, inherited condition is characterized by short stature, a skin rash that develops after sun exposure, infertility, and an increased risk of malignancy.
Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
Bloom syndrome is a rare, inherited condition characterized by short stature, a skin rash that develops after sun exposure, infertility, and an increased risk of malignancy.
Affected individuals typically present with severe pre- and postnatal growth deficiency and sparse subcutaneous fat throughout infancy and childhood. Most are less than the 97th percentile, when compared to the general population for both height and weight, and are rarely taller than five feet as adults. Other characteristic features include a high-pitched voice, learning disabilities, and distinctive facial features, such as a long and narrow face, retrognathia, and prominent nose and ears. Those affected with Bloom syndrome also have an increased risk of diabetes, chronic obstructive pulmonary disease (COPD), gastroesophageal reflux, and mild immune system dysfunction. Adult males with Bloom syndrome are infertile due to lack of sperm production; adult women have reduced fertility and experience menopause unusually early.
Upon sun exposure, those with Bloom syndrome develop a red rash over the nose and cheeks in a butterfly-shaped pattern. A skin rash can also appear on other areas typically exposed to the sun, such as the back of the hands and the forearms. Telangiectases often appear within the rash and can also occur in the eyes. Other skin features include hypopigmentation or hyperpigmentation on areas of skin protected from sun exposure.
Bloom syndrome is associated with an increased risk of cancer. Cancer types are diverse and include, but are not limited to, various carcinomas, lymphomas, and leukemia. Cancers typically occur earlier in life compared to the general population, and more than one cancer type may develop in the same individual.
Due to the rarity of Bloom syndrome, the specific lifetime risk of developing BLM-related tumors is unknown. See the table below for the incidence of various malignancies among 205 affected individuals, as collected from the Bloom’s Syndrome Registry from 1954 to 2012.
|Cancer type||Age range at diagnosis (years)||Number||Percent|
|Lower enteric tract||16-49||30||14.6%|
|Upper entero/respiratory tract||25-48||22||10.7%|
|Genitalia and urinary tract||<1-43||17||8%|
|Lower respiratory tract||26-40||9||4.3%|
|Acute lymphoblastic leukemia||5-40||12||5.8%|
|Acute myelogenous leukemia||2-47||25||12.2%|
|Connective tissue (sarcoma)||4-30||4||2%|
|Central nervous system (brain)||3||1||0.5%|
|Primary site unidentified, metastatic||28-33||3||1.5%|
Analysis of the BLM gene identifies pathogenic variants in 90% of affected individuals.
Bloom syndrome is inherited in an autosomal recessive pattern.
Bloom syndrome is overall a rare condition; however, the carrier frequency among the Ashkenazi Jewish population in New York City and Israel is approximately 1%.
Analysis of the BLM gene may be considered in individuals with the following:
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|