The Sequence 11/14-11/20
A Selection of Topics on Neurological Disorders, Direct to Consumer Testing, and Cancer from the 2022 National Society of Genetic Counselors Conference
Hello from Nashville! In this special edition of The Sequence, I will be recapping highlights from the National Society of Genetic Counselors (NSGC) 41st Annual Conference, which took place November 16-20 in Nashville, TN. It may be the most genetic-counselor-y newsletter yet.
Neurological disorders
Potential new treatment for prion disease
Prion diseases are diseases in which prion protein (PrP), a protein in the brain, is misfolded, causing progressive neurological diseases. The progressive neurological disorders impair brain function, cause changes in memory, personality, and behavior; cause a decline in intellectual function and memory; and can cause abnormal movements. Between 10 and 15 percent of all cases of prion disease are caused by mutations in the PRNP gene.
The news: A new drug may be available soon. The concept is that it will lower the amount of regular prion protein, decreasing the amount of protein that the misfolded prion protein can grab, therefore lowering the amount of misfolded prion protein in the brain. This is a severe disorder that can cause deterioration of the brain in a matter of months, and a treatment may be coming soon.
Additional resources: Genetic counseling for prion disease, prionregistry.org
Patient/Pharma partnership in genetic prion disease was presented at NSGC by Sonia Vallabh
Resources for genetic testing, counseling and research on ALS
ALS is is a progressive disease that affects motor neurons, which are specialized nerve cells that control muscle movement. It is a subtype of motor neuron disease (MND). The International Alliance of ALS/MND Associations believes that patients should have access to care, up-to-date education about clinical genetics in ALD/MND, genetic counseling, genetic testing, and treatment, and that relatives should have the same access. Check out this infographic about the genetics of ALS/MND. You can check out my previous post on some of the latest research about specific genetic mutations that can cause ALS here.
Collaboration as a Catalyst was presented at NSGC by Catherine Cummings, Executive Director The International Alliance of ALS/MND Associations
Genetic testing for Huntington’s Disease
Huntington's disease is a rare, inherited disease that causes the progressive breakdown of nerve cells in the brain. Huntington's disease has a wide impact on a person's functional abilities and usually results in movement, cognitive and psychiatric disorders. There are very specific guidelines for Huntington’s disease. However, the current model is only supported in 55 centers of excellence around the country. This means testing is not actually accessible to most people, and so most people are still getting testing done with their primary care provider, leaving gaps in the screening and counseling process. Well, there’s a new solution in town: HD Genetics. This new company provides all of the resources needed for testing for Huntington’s disease without the drive to a center of excellence.
Improving Access to Huntington’s Disease Genetic Counseling & Testing was presented at NSGC by BJ Viau Founder, HD genetics
Direct-to-consumer testing
Direct-to-consumer (DTC) testing has become more popular with the evolution of companies like 23andMe and Ancestry, through which individuals have the power to order genetic testing from the comfort of their home to learn their ancestral background, fun traits like sweet vs. salt taste preferences , and even some health risks like risk for breast cancer based on certain BRCA variants. The talks highlighted here looked at patient perspectives on some of these tests as well as their utility in diagnosing medical conditions.
DTC genetic testing for Alzheimer’s Disease
Direct to consumer tests like 23andMe have the ability to identify and report a susceptibility to develop Alzheimer’s disease. Alzheimer’s disease is a form of dementia causing memory loss and change in cognition and behavior after age 75 due to the accumulation of certain proteins in the brain. DTC testing is generally looking for and identifying what we call the homozygous E4 allele in the APOE gene. Individuals that are homozygous for the E4 allele in the APOE gene are at an increased risk for Alzheimer’s. It causes a 10-15% increased risk for Alzheimer’s over the general population. To help support patients through the identification of this risk, these guidelines were published that recommended that genetic counselors and health care providers don’t offer genetic testing for Alzheimer’s (i.e. the E4 allele), and they specify that if genetic testing is offered, patients should receive proper counseling and follow up with a team of providers. This process is compared to genetic testing for Huntington’s disease, described in the above section. Although logical in 2011 when these guidelines were published, in the era of DTC testing in which patients can find out the risks for Alzheimer’s themselves, it may be time for providers to re-think their comfortability in offering this genetic testing, which patients can seek elsewhere on their own. Simply put, some people want to know their risks, and it’s important to be a part of the conversation rather than resist it. Timely, since Chris Hemsworth just found out he is homozygous for the E4 allele and is encouraging others to know their risks.
Genetic Testing for APOE: Taboo or To-Do was presented at NSGC by Emily Brown, CGC, Tara Hart, CGC, Laynie Dratch, CGC, Stephanie Ashley, CGC, and Hannah Ison, CGC
Utility of consumer-initiated testing for newborns.
Newborn screening (NBS) is a routine procedure for which babies are given a prick to their heels 24-48 hours after they’re born to collect a blood sample. That sample is used to test for a number of rare, severe genetic disorders that have effective treatments. Fulgent genetics studied the utility of a panel of 255 genes, initiated by parents of healthy babies, to see if any diagnoses would be identified in these healthy babies. Results showed positive genetic findings in 4% (n=19) of babies tested. Of the 11 genes with mutations identified in these babies, 6 were not on NBS (and therefore wouldn’t have been identified if it weren’t for this test). This tells us that consumer initiated genetic analysis of newborns can most certainly result in clinically actionable genetic diagnoses, even after NBS. See my previous post on pilot studies of expanded NBS for more foundational information on NBS.
Clinical Utility of Consumer-Initiated Newborn Genetic Analysis was presented at NSGC by Han Chao
Considering patient perspectives on direct to consumer testing
When studying patients who received DTC pharmacogenetic screening, or screening of genetic variants that affect the way we metabolize drugs, and testing for secondary findings, or findings for late-onset actionable conditions (think screening for cancer or heart disease), most patients had different expectations of the testing than what the testing actually provided. When surveyed, most patients agreed to a statement citing that testing would look at the medical conditions they were concerned about. But, when asked what things they were concerned about, only 1% of those conditions could actually be identified on the test. Another 50% could be on the test, but a negative test would not mean there’s no genetic cause, and a whopping 41% were not on the test at all. DTC is an exciting way to empower people to understand their health, but proper counseling around what the testing can and can’t do may be warranted.
What do patients expect to learn from preemptive population genetic testing? Data from Imagenetics METRICS was presented at NSGC by Megan Bell, CGC
Cancer
The breakdown of cancers caused by mutations in CHEK2
CHEK2 is an appropriately named ‘checkpoint’ gene. It helps to repair DNA that is damaged, and so mutations cause it to not work properly, leading to DNA damage and eventually cancer. It’s a gene that we’ve known causes a susceptibility to breast cancer for a while, and have been continuously learning more about what other cancers it can cause such as pancreatic, colorectal, and other cancers, and at what prevalence. This study by Memorial Sloan Kettering looked at a cohort of 16,172 patients with cancer to see who had pathogenic CHEK2 mutations, and what types of cancer they had. They found 3% prevalence of CHEK2 mutations in gastric cancers, 1.5% prevalence in pancreatic, colorectal, and other cancers, and 1.8% prevalence in non-CHEK2-related cancers. These numbers decreased when taking out patents with the common I157T variant, a controversial genetic variant considered pathogenic (disease-causing) by some labs but not others. Single-gene causes for cancers is one of the most powerful ways to assess for risk based on personal and family history, so every gene we can learn more about is helpful in the road to early diagnosis and cancer prevention in some individuals.
Distribution of gastrointestinal tumors seen in cancer patients with germline pathogenic or likely pathogenic variants in CHEK2 was presented at NSGC by Sarah Kane, CGC
Treatment and prevalence of breast cancer in black women
To begin, it’s important to understand the recent groundbreaking guidelines that recently came out by the NCCN (National Comprehensive Cancer Network), the organization whose guidelines are followed by a majority of oncologists and oncological healthcare providers follow in the management of cancer: All women with breast cancer under 50 years old should get germline genetic testing. A discussion on this could be the topic of an entire newsletter on its own, but for now, we will continue on the topic at hand. If it is recommended that all women under 50 with breast cancer receive genetic testing, are there still differences in the treatment of young black women with breast cancer? This study by Dr. Maya Roberson says yes. In a study of 608 black women under 50 years old with breast cancer, only half received genetic testing. The most common reason cited for not receiving genetic testing was that they were not offered genetic testing. This supports other things we already know about this underserved population, who are 40% more likely to die from breast cancer than their white counterparts. This increase in mortality in the black population of women with breast cancer has been associated with being diagnosed in later stages of progression of the condition, underscoring the importance of taking preventative measures like genetic testing to assess for cancer risk.
Now, after digesting that for a moment, I have more news. This time it comes from Dr. Melissa Davis, who believes there is in fact a biological component to the prevalence of breast cancer in black women; especially an aggressive form of breast cancer we call triple negative. Dr. Davis describes an increase in immune response mediating cells in the African American population that may be contributing to the higher prevalence of triple negative breast cancer (TNBC). In studying across populations stemming from Africa, she saw increased instances of these immune cells in African American and Ghanayan populations, while in Ethiopia, for example, genetic variation in tumors looked like cancer tumors identified in the European population. She notes higher prevalence of the ‘Duffy-null’ allele, and higher spikes of inflammation whenever the Duffy-null expressed. We wouldn’t have identified this allele before when looking at previous GWAS studies, which focused on genetic variation in European populations. There is a lot more work to be done to address the disparity of care in black women with breast cancer, and understanding the biology underlying an aggressive type of cancer seen in this population is an important first step.
Breast Cancer treatment patterns in Black women aged ≤50 by germline testing and results was presented at NSGC by Dr. Maya Roberson, and Biological Mechanisms of Disparities in Cancer Risk and Clinical Outcomes of Cancer Diagnoses was presented at NSGC by Dr. Melissa Davis
Hope you enjoyed this special edition! The Weekly Sequence will be back as you know it next week.