Bloom's Syndrome via the BLM Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture ProbesTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
3089 | BLM | 81479 | 81479,81479 | $640 | Order Options and Pricing |
Pricing Comments
This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
Turnaround Time
3 weeks on average for standard orders or 2 weeks on average for STAT orders.
Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics 
Clinical Features
Bloom’s syndrome (BS; OMIM 210900) was first described in 1954 as a “congenital” skin disorder in “dwarfs” (Bloom Am J Dis Child 88:754-758, 1954). While patients were found to have additional clinical features, such as immune deficiencies and a propensity for cancer (German et al. Science 148:506-507, 1965; German Am J Hum Genet 21-196-227, 1969), sun-sensitive facial lesions, low birth weight and stunted growth remain the most consistent features of Bloom’s syndrome today. Symptoms of BS are related to increased mutability of proliferating somatic cells, particularly epithelial cells and lymphocytes. When grown in culture and viewed microscopically, cells of BS patients exhibit extensive “chromosome breakage”, including gaps and breaks, structural rearrangements, and telomeric associations (German and Crippa Ann Genet 9143-154, 1966). Chromosome breakage ultimately leads to excessive somatic recombination and high variant rates (Groden and German Hum Genet 90:360-367, 1992). About one-third of individuals with BS die by the age of 30 due to complications of cancer or from chronic lung disease as a result of immune deficiency (German Cancer Genet Cytogenet 93:100-106, 1997).
Genetics
Bloom’s syndrome is an autosomal recessive disorder, caused by homozygous or compound heterozygous variants in the BLM gene (German et al. Hum Mutat 28:743-753, 2007); more than 60 unique variants have been identified. Most (60%) are single nucleotide changes leading to nonsense, missense, or splicing variants, while the remaining are small insertions or deletions (35%) or large deletions of multiple exons (5%). The BLM gene encodes a DNA helicase of the RecQ family. RecQ proteins are critical for maintaining the efficiency and integrity of DNA replication (Hickson Nat Rev Cancer 3:169-178, 2003); they resolve secondary structures ahead of replication forks, limit recombination to identical sequences, and assist in the replication and maintenance of telomeres (Bennett and Keck Crit Rev Biochem Mol Biol 39:79-97, 2004). In addition to these cellular functions, the BLM protein may also be important for the mismatch repair (MMR) pathway through its interaction with the MLH1 and MSH6 proteins (Langland et al. J Biol Chem 276:30031-30035, 2001; Pedrazzi et al. Biol Chem 384:1155-1164, 2003). Indeed, there is some evidence that heterozygous carriers of a BLM variant have an increased risk for colorectal cancer (Gruber et al. Science 297:2013, 2002), a disease most commonly associated with heterozygous variants in the MMR genes MLH1, MSH2 and MSH6.
Clinical Sensitivity - Sequencing with CNV PG-Select
In a retrospective study (German et al. Hum Mutat 28(8): 743-53, 2007), 87% of patients diagnosed with Bloom’s syndrome were reported to have two BLM variants. In 6% of the patients, only one variant was found for this recessive disease, indicating the second variant was not detectable by DNA sequencing methods.
Gross deletions of multiple exons account for approximately 5% of BLM cases.
Testing Strategy
This test provides full coverage of all coding exons of the BLM gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Candidates for this test are patients diagnosed with Bloom’s syndrome. This test is specifically designed for heritable germline variants and is not appropriate for the detection of somatic variants in tumor tissue. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in BLM.
Candidates for this test are patients diagnosed with Bloom’s syndrome. This test is specifically designed for heritable germline variants and is not appropriate for the detection of somatic variants in tumor tissue. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in BLM.
Gene
Official Gene Symbol | OMIM ID |
---|---|
BLM | 604610 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Disease
Name | Inheritance | OMIM ID |
---|---|---|
Bloom Syndrome | AR | 210900 |
Citations 
- Bennett RJ, Keck JL. 2004. Structure and function of RecQ DNA helicases. Crit. Rev. Biochem. Mol. Biol. 39: 79-97. PubMed ID: 15217989
- Bloom, D. 1954. Congenital telangiectatic erythema resembling lupus erythematosus in dwarfs; probably a syndrome entity. AMA Am J Dis Child 88(6): 754-8. PubMed ID: 13206391
- German and Crippa Ann Genet 9143-154, 1966
- German J, Sanz MM, Ciocci S, Ye TZ, Ellis NA. 2007. Syndrome-causing mutations of the BLM gene in persons in the Bloom’s Syndrome Registry. Human Mutation 28: 743–753. PubMed ID: 17407155
- German, J. (1997). "Bloom's syndrome. XX. The first 100 cancers." Cancer Genet Cytogenet 93(1): 100-6. PubMed ID: 9062585
- German, J. 1969. Bloom's syndrome. I. Genetical and clinical observations in the first twenty-seven patients. Am J Hum Genet 21(2): 196-227. PubMed ID: 5770175
- German, J., et.al. 1965. Chromosomal Breakage in a Rare and Probably Genetically Determined Syndrome of Man. Science 148: 506-7. PubMed ID: 14263770
- Groden, J., German, J. (1992). "Bloom's syndrome. XVIII. Hypermutability at a tandem-repeat locus." Hum Genet 90(4): 360-7. PubMed ID: 1483691
- Gruber SB, Ellis NA, Scott KK, Almog R, Kolachana P, Bonner JD, Kirchhoff T, Tomsho LP, Nafa K, Pierce H, Low M, Satagopan J, et al. 2002. BLM heterozygosity and the risk of colorectal cancer. Science 297: 2013.. PubMed ID: 12242432
- Hickson ID. 2003. RecQ helicases: caretakers of the genome. Nature Reviews Cancer 3: 169–178. PubMed ID: 12612652
- Langland G. 2001. The Bloom’s Syndrome Protein (BLM) Interacts with MLH1 but Is Not Required for DNA Mismatch Repair. Journal of Biological Chemistry 276: 30031–30035. PubMed ID: 11325959
- Pedrazzi G, Bachrati CZ, Selak N, Studer I, Petkovic M, Hickson ID, Jiricny J, Stagljar I. 2003. The Bloom’s syndrome helicase interacts directly with the human DNA mismatch repair protein hMSH6. Biol. Chem. 384: 1155–1164. PubMed ID: 12974384
Ordering/Specimens 
Ordering Options
We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.
myPrevent - Online Ordering
- The test can be added to your online orders in the Summary and Pricing section.
- Once the test has been added log in to myPrevent to fill out an online requisition form.
- PGnome sequencing panels can be ordered via the myPrevent portal only at this time.
Requisition Form
- A completed requisition form must accompany all specimens.
- Billing information along with specimen and shipping instructions are within the requisition form.
- All testing must be ordered by a qualified healthcare provider.
For Requisition Forms, visit our Forms page
Specimen Types
Specimen Requirements and Shipping Details
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
STAT and Prenatal Test Options are not available with Patient Plus.
No Additional Test Options are available for this test.