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).
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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 January 2017, Gene. Gene ID : 641. https://www.ncbi.nlm.nih.gov/gene/641. Accessed January 2017).
Individuals with a single pathogenic variant in BLM have a 50% chance of passing that variant on to their offspring. Once a variant is detected in an individual, it is possible to identify at-risk relatives who can pursue testing for this specific familial variant. For there to be a risk of Bloom syndrome in offspring, both parents would each have to have a single pathogenic variant in BLM and in such a case, the risk of having an affected child is 25%.
Medical management guidelines and surveillance recommendations
Medical management and surveillance protocols for individuals with a single pathogenic variant in BLM have been developed by the National Comprehensive Cancer Network® (NCCN®) (NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Colorectal. Version 2.2016):
If there is no personal history of colorectal cancer but an individual has an affected first-degree relative, colonoscopy is recommended every 5 years beginning at age 40, or 10 years prior to the first-degree relative’s age at diagnosis.
If there is no personal history of colorectal cancer and no diagnosis of colorectal cancer in a first-degree relative, colonoscopy is recommended every 5 years beginning at age 40.
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, as well as 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.
Review date: February 2017
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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.
Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.
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