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BLM

Alias

BS; RECQ2; RECQL2; RECQL3

Associated disorders

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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BLM

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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

Clinical condition
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.

Gene information
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).

Inheritance
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.

Additional reference
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

Assay and technical information

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.

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.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
BLM NM_000057.3