BS; RECQ2; RECQL2; RECQL3
The BLM gene is associated with autosomal recessive Bloom syndrome (MedGen UID: 2685). Additionally, the BLM gene has preliminary evidence supporting a correlation with autosomal dominant colorectal cancer in individuals who carry a single pathogenic variant (PMID: 12242432, 26358404, 12702560, 18210922).
Order this gene as a single gene test.
Invitae tests that include this gene:
The gene BLM encodes a RecQ helicase protein. Helicases unwind DNA so that it can be it can be replicated in preparation for cell division. The BLM protein helps maintain the stability and structure of the DNA during this process. Loss of BLM function results in chromosomal breaks and rearrangements; creating pathogenic variants that contribute to cancer progression, immunodeficiency, and other symptoms.
BLM – Bloom Syndrome
MedGen UID: 310484, 2685
The BLM gene is associated with autosomal recessive Bloom syndrome. This is a rare, chromosomal instability condition that results when an individual inherits a pathogenic variant from each parent. Features include growth deficiency, sun-sensitive skin rash, infertility, and an increased risk of malignancy (PMID: 23225144, 20301572).
While individuals with a single pathogenic BLM variant do not have Bloom syndrome, there is evidence they may have an increased risk of colon cancer (PMID: 12242432, 19945966, 26778106, 26358404, 18210922, 12702560). Therefore, BLM is available as a “preliminary evidence” on Invitae’s Colorectal Cancer Panel. Preliminary evidence genes are selected from an extensive review of the literature and expert recommendations, but the association between the gene and the specific condition has not been completely established. This uncertainty may be resolved as new information becomes available, and therefore clinicians may continue to order these preliminary evidence genes.
The BLM gene is part of the RecQ helicase family, known as the “caretakers of the genome”. Helicases play a role in maintaining genomic stability by regulating DNA replication, DNA damage repair, and suppression of inappropriate sister chromatid exchange (PMID: 24096176; Genetics Home Reference. BLM gene: https://ghr.nlm.nih.gov/gene/BLM. Accessed February 2018; Gene ID: 641. https://www.ncbi.nlm.nih.gov/gene/641. Accessed February 2018).
Bloom syndrome has autosomal recessive inheritance, and affected individuals have two pathogenic variants—one in each copy of their BLM genes. Affected individuals will pass one pathogenic BLM variant to all of their children. For there to be a risk of Bloom syndrome in offspring, both the patient and his/her partner would each have to carry a pathogenic variant in BLM. In this case, the risk of having have an affected child would be 25%.
Medical management guidelines and surveillance recommendations
Because the evidence regarding BLM heterozygotes and colon cancer risk is limited and preliminary, there are no guidelines or recommendations to suggest alterations to medical management based solely on the presence of a pathogenic BLM variant. However, an individual’s cancer risk and medical management are not determined by genetic test results alone. Overall cancer risk assessment incorporates additional factors, including personal medical history, family history, and any available genetic information that may result in a personalized plan for cancer prevention and surveillance.
It is advantageous to know if an individual has a pathogenic variant in BLM. At-risk relatives can be identified, allowing the pursuit of a diagnostic evaluation. In addition, the available information regarding hereditary cancer susceptibility genes is constantly evolving and more clinically relevant BLM data is likely to become available in the near future. Awareness of this condition allows patients and their providers to be vigilant in maintaining close and regular contact with their local genetics clinic in anticipation of new information, inform at-risk family members, and diligently follow recommended screening protocols.
Referenced with permission from the NCCN Genetic/Familial High-Risk Assessment: Colorectal. Version 3.2017. © National Comprehensive Cancer Network, Inc. 2016. All rights reserved. Accessed February 2018. To view the most recent and complete version of the guideline, go online to NCCN.org.
The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a statement of consensus of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
Review date: February 2018
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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.
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|