Gene Scene Blogs

As we celebrate GGC’s 50th anniversary, we will publish monthly ‘Then & Now’ blog posts throughout 2024.
This month we’re taking a look at the growth of GGC’s clinical services.
Follow along with us as we reminisce!

Helping patients is our driving force. Being able to serve patients across all of South Carolina is just the icing on the cake! And this all starts with patients having ACCESS to genetic health services. South Carolinians have not always had easy access to clinical genetics, and the journey to get where we are today has not always been the easiest, but it has been worth it! Continue reading to see how the Greenwood Genetic Center (GGC) laid the foundation for accessible clinical genetic services in South Carolina.

GGC was established in 1974. Before then, the Medical University of South Carolina (MUSC) in Charleston had the only genetics clinic in the state. When clinical geneticist Dr. Wladimir Wertelecki left MUSC in 1974, it left a hole in the state – paving the way for GGC to establish accessible genetic healthcare throughout South Carolina.

GGC co-founder Dr. Roger Stevenson recognized the need to reach patients beyond Greenwood, and satellite clinics began to take shape in 1975 across the Coastal, Midlands, Pee Dee, and Piedmont regions of South Carolina. In close partnership with the SC Department of Disabilities and Special Needs, GGC clinicians regularly traveled across the state to serve patients from every county of SC, sometimes even renting a small plane for more distant clinics. Dr. Stevenson initially served as the sole geneticist with case workers, genetic associates, and genetic counselors organizing clinics, testing, and follow-up.

Over time, GGC’s presence throughout the state was strengthened with the addition of Dr. Richard Schroer, Dr. Robert Saul, and Dr. Curtis Rogers, along with genetic counselors, support staff, and other faculty members. Satellite offices in Columbia and Greenville opened in 1988, followed by Florence in 2004, and Charleston in 2007. The strategically located clinics made access to genetic care easier for all South Carolinians.

Today, ensuring access to genetics care remains the top priority. What began as small teams traveling the state has culminated to fully-staffed clinics with doctors, advanced practice practitioners, nurses, psychologists, clinical trial coordinators, genetic counselors, genetics assistants, and support staff. Each team member has their own skill set to provide patients with comprehensive care in the field of genetics and genomics. In the last fiscal year, our clinical team saw 5,325 patients! The clinics can even offer telehealth appointments and eVisits to give patients access to genetics without having to the leave home.

It was not too long ago that treatment options for genetic disorders were almost nonexistent. Now, geneticists are able to provide treatments such as enzyme replacement therapy for patients with lysosomal storage disorders, medication for conditions including achondroplasia and Friedrich’s ataxia, and even gene therapy for disorders like spinal muscular atrophy and sickle cell anemia. Most notably, our clinic recently participated in a clinical trial which led to the FDA approval of DAYBUE^TM, the first and only drug to specifically treat patients with Rett syndrome.

No discussion of the clinics would be complete without the mention of the internationally-known Genetic Counseling Aids, or the Greenwood “flip book.”  In the 1980s, Dr. Schroer, a full-time clinical geneticist, was also responsible for the educational programs and materials at GGC. In 1984, the first edition of the Genetic Counseling Aids was published by Dr. Schroer, Dr. Hal Taylor, and Dr. William Potts. They were designed to help clinicians explain complex genetic concepts through simplified visual aids.

The Counseling Aids started with 34 pages. Now, in its 7th edition with 97 pages, GGC’s Counseling Aids are used by geneticists, genetic counselors, and other providers all over the world to help patients and their families understand complex topics such as inheritance patterns, inborn errors of metabolism, hereditary cancer, and genetic testing. Take it from this non-science major – THEY HELP!

In 2023, GGC established a Precision Medicine Initiative with four pillars (Access, Analysis, Answers, and Action) with the goal of providing patients with the right treatment at the right time. But even with all of the amazing technologies at hand and the promise of new treatments, none of that matters if patients don’t have ACCESS.  Our Precision Medicine Initiative perfectly complements our 50 year effort to reach patients, remove barriers, and provide families with the innovative and compassionate care they all deserve.

 

Post by Caroline Pinson

As we celebrate GGC’s 50th anniversary, we will publish monthly ‘Then & Now’ blog posts throughout 2024.
This month we’re taking a look at the growth of GGC’s physical spaces.
Follow along with us as we reminisce!

Growing up in Greenwood, I always knew what was at the end of Liner Drive – the Children’s Clinic. It was where I would go see my pediatrician, Dr. Skinner for check-ups and illnesses. Fast forward ??? years later – you can do the math – I’m now working at the end Liner Drive, but this time it’s the Greenwood Genetic Center (GGC) on Gregor Mendel Circle at the end of that road.

So how did GGC evolve from a small building on Spring Street to a 50-acre campus with four buildings surrounded by another 140 acres?

Let me explain.

The first GGC facility

Dr. Roger Stevenson & Dr. Hal Taylor were fellows together at Johns Hopkins University, where they dreamed of working in a patient-centered genetics program with state-of-the-art technology. When joining an established medical school didn’t pan out (remember this was in the infancy of medical genetics, it was not the big deal it is today), they took another route – establishing an independent center. In 1974, with support from Jim Self and the state of South Carolina, their dream was finally realized in the form of the Greenwood Genetic Center.

GGC started in a 7500 square foot building on Spring Street built to house clinic and office space, a chromosome lab, and even a library (this was before the internet, folks).

The Current Campus

The Center’s reputation grew, and as services expanded, the need for a larger, more specialized facility became apparent. In 1980, GGC relocated to its current site on Gregor Mendel Circle. GGC’s first building on the current campus housed the diagnostic labs. A few years later, in 1984, the clinic building joined the growing campus.

GGC’s growth didn’t stop there. Under the direction of Dr. Charles Schwartz, the Division of Research was formed in 1989. The diagnostic and research divisions shared laboratory space in the original lab building until 1996, when the JC Self Research Institute for Human Genetics building was completed.

The discoveries made in this building led to  GGC’s international reputations in research on X-linked intellectual disability, birth defects, and other rare diseases. In addition to laboratory space for the research team, this building houses the Senator William O’Dell Boardroom, the Klauber Library, the Curry Conference Center, GGC Foundation offices, and the Hazel & Bill Allin Aquaculture Facility. The aquaculture facility came to GGC in 2018 with Drs. Richard Steet and Heather Flanagan-Steet when they joined GGC to lead research efforts following Dr. Schwartz’s retirement.

In 2009, GGC reached another milestone with the opening of the South Carolina Center Treatment of Genetic Disorders (the Treatment Center), a state-of-the-art facility dedicated to advancing the treatment for genetic disorders. When the Treatment Center (where I work) opened, the clinic and diagnostic labs moved in. The former lab building is still home to one of GGC’s lab – array, the rest of the building was converted to a Genetic Education Center for visiting students.  The former clinic is now the dedicated home for our amazing administrative folks – billing, IT, HR, and finance.

Our statewide presence

GGC is a statewide organization serving patient across all of South Carolina. In the early years, that meant our clinicians traveled to every county in the state to hold clinics. As our patient population grew, we needed a better way to reach those outside of the Greenwood area. In 1988, GGC opened two satellite clinic offices – one in Greenville and one in Columbia. A Florence office followed in 2004, and we expanded into Charleston in 2007. This made our clinic operations more efficient and significantly improved patient access for those all across the Palmetto State.

Wow! That’s quite impressive growth! But wait there’s more!

Beyond GGC

GGC’s campus and the surrounding 140 acres are a part of greater concept: the Greenwood Genetic Center Partnership Campus. With GGC being the anchor of the Partnership Campus, the campus offers location opportunities for bioscience companies and institutions that are committed to advancing scientific knowledge, promoting patient care, and collaborative initiatives. Clemson University took us up on that opportunity, and in 2018, the Clemson Center for Human Genetics (CHG) opened.

The Clemson CHG is led by world-renowned geneticist, Dr. Trudy Mackay. She leads a research team that focuses on genetic and environmental risk factors for a range of human diseases by using fruit flies as the model organism. The collaboration between GGC and Clemson CHG has led to funding from the NIH’s COBRE program (Center for Biomedical Research Excellence). Even this gamecock is proud to have Clemson on campus!

One advantage of working here is that we are able to enjoy the beautiful campus (fall is my favorite). Dr. Stevenson and Dr. Taylor started GGC with a vision; founding board member and long-time friend of the Center, Dr. Bill Klauber, believed in their vision. Upon Dr. Klauber’s passing, his estate provided funds to enhance the campus. In 2015, the Klauber Plaza was constructed in the center of campus to provide, “…beauty that would inspire vision for all those who saw it.”

Today, employees on the Greenwood campus enjoy the fountain and amazing sculptures when walking from building to building and the occasional picnic

 

If you are reading this and are a local Greenwoodian, ride down Liner Drive and stop at Gregor Mendel Circle (non-locals are also welcome!) Pack a picnic to enjoy on the Klauber Plaza, and admire this beautiful campus and reflect on how lucky we are that GGC calls Greenwood home.

Post by Caroline Pinson

 

As we celebrate GGC’s 50th anniversary, we will publish monthly ‘Then & Now’ blog posts throughout 2024.
Follow along with us as we reminisce!

A karyotype examines the number and structure of chromosomes – which are the packages for your DNA. There should be 46 chromosomes present in each cell, 23 from mom and 23 from dad. A karyotype was the first test offered by the diagnostic laboratory at GGC in 1974 and is still a common test today to diagnose conditions such as Down syndrome.

Bonne’ Lethco joined GGC as a technologist in the cytogenetics laboratory in 1989 and has spent the past 35 years preparing samples and analyzing chromosomes for thousands of patients.

When Bonne’ started working at GGC, preparing the samples was a very long and a very manual multistep process. She used a microscope to count each chromosome and took pictures with a camera mounted to the microscope (with actual camera film!). Then the film was developed and the images were enlarged in the lab’s dark room. Finally, Bonne’ physically cut out each chromosome in the picture and pasted each one in order on paper to make a karyotype for analysis. She completed the initial analysis before sending it to the lab director who completed the final analysis and signed out the report. You can only imagine how long of a process this was!

 

In 2016, the laboratory adopted a new technology, called CytoVision that reduced some of the hands-on manual steps and increased efficiency. CytoVision decreases the turnaround time and improves the resolution of chromosome images for better detection of abnormalities.

Bonne’ can now count each chromosome with a click of a mouse and digitally cut out each chromosome (think PhotoShop).  She ensures the computer does the karyotype correctly (yes, even computers make mistakes), and she still does the initial analysis before the director reviews it.

 

 

While some of the processes for chromosome analysis has remained the same over the years (culturing cells, staining slides, conducting the initial analysis); the biggest and best change Bonne’ has seen with the addition of new technology is the decrease in turnaround time. When the cytogenetics lab adopted CytoVision, patients and families could receive a diagnosis in days rather than weeks.

Bonne’ Gives Greater Care by helping provide a diagnosis. She takes pride in knowing that having the correct diagnosis can lead to more resources or treatments for the patient. And although how we do the test has certainly changed over the years, our most important work is constant: our commitment to helping find answers for patients and their families.

GGC welcomed first genetic counseling intern in the Division of Education

Training the next generation of genetic counselors is an important task for GGC. Each semester, genetic counselors-in-training spend weeks in one of GGC’s clinical offices to gain valuable experience in real-life clinical settings. They practice drawing pedigrees, coordinate genetic testing, and explain very complex concepts to patients and their families under the supervision of one of GGC’s exceptional board-certified genetic counselors.

But for the first time, GGC’s Division of Education had a genetic counseling intern. Coltrane Beck-Chance, a rising second-year genetic counseling student in the Master’s program at UNC Greensboro, spent his summer working with students, teachers, and GGC’s team of instructors.

UNC Greensboro’s genetic counseling program requires students to spend one of their rotations in a non-clinical setting to gain exposure to the growing opportunities for genetic counselors to pursue non-traditional roles.  Many students work with genetic research teams or in a genetic testing lab, but Coltane chose education.

“When I started my Master’s, I expressed an interest in a rotation where I had the opportunity to teach, and one of our faculty members suggested Greenwood Genetic Center,” said Coltrane. “This rotation allows me to be exposed to clinical genetic counselors who are able to work in community outreach and education.”

During his six weeks with GGC, Coltrane has observed and assisted with hands-on STEM activities on board the Gene Machine mobile science lab. He also developed a presentation about the ethics of genetic testing with science teachers at GGC’s summer workshop and shared his journey to becoming a genetic counselor with high school students during GGC’s summer camp. He has also worked remotely on other projects including an educational blog about the genetics of Alzheimer’s disease and a review of GGC’s Counseling Aids book.

“We were thrilled when Coltrane reached out and proposed this rotation,” said Leta Tribble, PhD, Director of Education at GGC. “While most people think of genetic counselors in terms of their direct patient care roles, they are skillfully trained to translate complex medical information which makes them natural educators for other populations as well, including students, teachers, and other healthcare professionals.”

“There are so many transferable skills between education and working in the genetics clinic,” said Coltrane. “As I am presenting to a class, I am able to learn in real-time if my explanations of difficult topics are making sense. Tailoring to my audience is one of the most important things I will learn to do- to make sure that my patients are getting the most out of the session.”

“We rely on our team of genetic counselors to support our educational efforts, and many are involved in our outreach efforts such as leading activities for STEM events, lecturing for medical students, and working with our summer camps,” added Tribble. “We hope that this summer will prove to be eye-opening and educational for Coltrane, and will enhance his skills as a genetic counselor.”

“At my middle and high school, we did not have the opportunity for the kind of hands-on lab exposure that GGC’s programs provide,” added Coltrane. “I am hoping that my presentations and the genetics education that GGC provides will inspire young people to become genetic counselors. I look forward to these students being my colleagues in the future.”

At age 11, Aaron Ritz woke up with side pain. His pediatrician sent him to the hospital where he was found to be in complete renal failure. He started dialysis the next day.

“Aaron was diagnosed with polycystic kidney disease, which he likely had from birth, but aside from being small for his age, we had no signs that anything was wrong,” said Aaron’s mother Brandy Ritz. “In less than 24 hours, our world was turned completely upside down.”

There are two forms of polycystic kidney disease (PKD). The autosomal dominant form affects approximately 1/1000 individuals. It typically presents in adulthood and is most often caused by a single genetic mutation in one of two genes, PKD1 or PKD2. The autosomal recessive form of PKD is less common (1/20,000) and presents prenatally or in early childhood with two mutations within the same gene.

Aaron’s nephrologist suggested genetic testing due to the unusual nature of his clinical presentation, so he was seen at the Greenwood Genetic Center. Testing revealed no mutations in the genes most commonly associated with polycystic kidney disease, but he did have a single variant in a gene called NEK8.

“NEK8 is known to be a rare cause of autosomal recessive PKD when there are two mutations present, and typically there are also other extra-renal manifestations such as liver and pancreatic involvement,” said Rich Steet, PhD, Director of Research at the Greenwood Genetic Center (GGC). “But Aaron, who had no other organ involvement, only had a single genetic change in NEK8 which had never been associated with kidney disease.”

Given the puzzling results, Steet embarked on additional research testing to try and clarify this unexpected finding. By reaching out to other genetic testing laboratories and using GeneMatcher, an online tool that connects clinicians and researchers who have an interest in the same gene, Aaron’s genetic evaluation grew into a major international collaboration. Steet connected with geneticists in the US, the Netherlands, the United Kingdom, Canada, Belgium, Denmark, the Czech Republic, and Romania, and ultimately identified 21 individuals within 12 families who had both polycystic kidney disease and a single variant in NEK8. All of these patients also had a second normal copy of the NEK8 gene.

Numerous additional experiments were conducted by the collaborative group to confirm that these single variants were causative for PKD and to better understand how they cause kidney disease.

“Our experiments suggest that the genetic variants identified alter the NEK8 protein function in a very specific way,” said Steet. “It appears that the abnormal protein produced by the NEK8 variant in these families prevents certain other proteins from moving to cilia, structures in kidneys that help them function normally. When these proteins fail to localize to the cilia, severe cystic kidney disease develops.”

After a rough disease course which included severe hypertension, a stroke, and the removal of both diseased kidneys, Aaron had a complicated, but ultimately successful kidney transplant at age 12 and now, at 16, is thriving.

“Aaron has a regimen of medications that he will have to take for the rest of his life, but he’s doing great – working a part-time job and playing golf for his high school team,” said Brandy. “It all happened so fast, we didn’t really have time to process what was going on at the time, but now, to have the worst behind us and to have a clear diagnosis means everything!”

Steet noted that this is important work that expands our understanding of both the NEK8 gene and polycystic kidney disease. “In the future, clinicians should pay attention to single NEK8 variants in patients with PKD, include this gene in genetic testing panels, and consider the possibility of a single NEK8 variant as disease-causing,” added Steet.

The collaborators published these new findings in Kidney International, a journal of the International Society of Nephrology, in August.

 

Top photo: Aaron Ritz,11, during his first dialysis, less that 24 hours after his initial diagnosis, August 2018.

 

Bottom photo: Aaron,16, and his parents, Brandy and Jeremy Ritz, on a trip to Colorado, June 2023.

 

In 2022, Chris Hemsworth, best known for portraying Thor in the Marvel Cinematic Universe, released a show on Disney+ called Limitless. This show explored ways to combat aging and discover the full potential of the human body. However, in episode 5, the mighty Thor himself announced to the world that through genetic testing, he discovered that he had inherited two copies of the APOE ε4 risk alleles that increase the risk of developing Alzheimer’s disease. With this information, he decided to take a hiatus from acting. Hemsworth’s revelation has brought much attention to Alzheimer’s Disease and the APOE gene.

Alzheimer’s disease (AD) is a progressive type of dementia beginning with minor cognitive issues and progressing into severe and debilitating late-stage impairment. Most cases are late-onset, affecting people who are 65 or older. However, less commonly, AD can occur in younger individuals. The cause of Alzheimer’s disease is not fully understood. There are some changes to the brain – amyloid plaques and neurofibrillary tangles – that can be seen across most cases of Alzheimer’s disease that affect the function of neurons.

Alzheimer’s disease progresses across three stages…

1.  Early-stage Alzheimer’s: During this stage, the symptoms may be less obvious. People that are quite close to the patient, like a family member, may notice some changes such as difficulty with short-term memory (forgetting names and misplacing items); issues with planning and organizing; and difficulty completing tasks.
   This kind of short-term memory loss can happen to anybody, so it is important to pay attention to the frequency and patterns of these symptoms.
2.  Middle-stage Alzheimer’s: In this stage, which lasts the longest, symptoms will be more obvious and may include increasing difficulties with short-term memory; mood changes, like anger, frustration, and sadness; some personal long-term memory changes such as where they are from, their phone number, or their address; confusion about the date or where they are; sleep changes; trouble with bowel and bladder control; and needing help with daily activities, like hygiene, dressing, and preparing meals.
3.  Late-stage Alzheimer’s: During this stage, patients require significant assistance with daily life and may exhibit significant changes in abilities like walking, sitting, and eating; communication issues and inability to speak many words or phrases; vulnerability to certain infections like pneumonia; forgetting recent experiences, severe confusion, and lack of awareness of their surroundings.

Alzheimer’s Disease can have a genetic component.

Both early and late-onset Alzheimer’s can run in families, but most cases of AD are not familial. Approximately 25% of all Alzheimer’s disease cases are familial (3 or more relatives with AD), while 75% are non-familial.

Genes Causing Early-onset Alzheimer’s: We do know of three genes that are associated with early-onset Alzheimer’s: APP, PSEN1, and PSEN2. Changes in these genes (variants) are autosomal dominant, meaning that a patient only needs one copy of the variant in order to be affected. The APP and PSEN1 variants cause early-onset Alzheimer’s. However, the variant for PSEN2 is less penetrant, meaning not everyone who has a variant in this gene will go on to develop the condition, but their risk is still increased.

Genes Associated with Late-onset Alzheimer’s: There are also other genes that are known to influence an individual’s risk of developing Alzheimer’s. The most well-known of these genes is called APOE. Everybody has two copies of the APOE gene, and there are three different versions, or alleles: APOE ε2, ε3, or ε4.  If a person inherits two ε4 alleles (one from each parent), this can increase the risk for Alzheimer’s.

• For people with no APOE ε4 alleles, the average lifetime risk for AD is 10%. That increases if a first-degree relative (parent or sibling) has AD.
• For those with a single APOE ε4 allele, the risk of AD is 2-3 times higher
• For those with two APOE ε4 alleles, the risk is 2-10 times higher.

However, it is important to know that APOE alleles cannot determine for sure whether or not someone will develop AD. They are simply a risk factor.

While there are no specific recommendations on how to prevent AD, studies do suggest that with an active lifestyle, staying mentally active, and maintaining good heart health, the risk may be lessened.

APOE testing is not currently part of recommended clinical care; however, many direct-to-consumer genetic testing companies do offer this testing as part of their results. If you have testing and an increased risk is identified, you should speak with your healthcare provider or a genetic counselor to better understand what that result means for you.

 Guest blog author: Coltrane Beck-Chance, a genetic counseling summer intern at GGC from UNC Greensboro.
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References:

• Alzheimer’s Disease Genetics Fact Sheet. (n.d.). National Institute on Aging. Retrieved July 5, 2023, from https://www.nia.nih.gov/health/alzheimers-disease-genetics-fact-sheet
• Bird, T. D. (1993). Alzheimer Disease Overview. In M. P. Adam, G. M. Mirzaa, R. A. Pagon, S. E. Wallace, L. J. Bean, K. W. Gripp, & A. Amemiya (Eds.), GeneReviews®. University of Washington, Seattle. http://www.ncbi.nlm.nih.gov/books/NBK1161/
• Causes and Risk Factors for Alzheimer’s Disease. (n.d.). Alzheimer’s Disease and Dementia. Retrieved July 5, 2023, from https://alz.org/alzheimers-dementia/what-is-alzheimers/causes-and-risk-factors
• Goldman, J. S., Hahn, S. E., Catania, J. W., Larusse-Eckert, S., Butson, M. Barber., Rumbaugh, M., Strecker, M. N., Roberts, J. S., Burke, W., Mayeux, R., & Bird, T. (2011). Genetic counseling and testing for Alzheimer disease: Joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genetics in Medicine, 13(6), 597–605. https://doi.org/10.1097/GIM.0b013e31821d69b8
• Reitz, C., Tang, M.-X., Schupf, N., Manly, J. J., Mayeux, R., & Luchsinger, J. A. (2010). A Summary Risk Score for the Prediction of Alzheimer Disease in Elderly Persons. Archives of Neurology, 67(7), 835–841. https://doi.org/10.1001/archneurol.2010.136
• Stages of Alzheimer’s. (n.d.). Alzheimer’s Disease and Dementia. Retrieved July 4, 2023, from https://alz.org/alzheimers-dementia/stages
• What Happens to the Brain in Alzheimer’s Disease? (n.d.). National Institute on Aging. Retrieved July 5, 2023, from https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease

Family raises awareness for baby’s rare disease

When little Salem Marra was just six months old her parents, Joseph and Breanna, received devastating news. Their beloved baby girl had Leigh syndrome, a rare and lethal genetic disorder.

Breanna’s first concerns about baby Salem started during her first two months of life when she would have trouble feeding. She would gag and choke and sometimes had a hard time catching her breath. As part of her medical workup, Salem was seen by GGC’s Dr. Richard Schroer who, suspecting a mitochondrial disorder, ordered genetic testing. The test revealed that Salem had a change in a mitochondrial gene, mtATP6, which was found in all of her cells.

Mitochondria are the powerhouses of the cells. They produce the energy required by cells to do almost everything. When the mitochondria don’t function properly, the cells and the body are deprived of energy causing a variety of issues including feeding difficulties, poor muscle tone, lethargy, seizures, and developmental delays. Over time, the lack of energy output damages or destroys cells, especially those of the nervous system which require large amounts of energy to function properly. The average lifespan for a child with Leigh syndrome is just 2-3 years.

“The hardest part is walking around with smiles on our faces not knowing when our last moments with her could be,” shared Breanna.

Breanna carries the same mutation as Salem, but because it is only present in about half of her cells, she is able to produce enough energy to remain asymptomatic.

With mounting medical bills, the Marra family started a GoFundMe account and shares Salem’s story on social media to raise awareness for this rare disorder.

“We just want to bring a focus to rare diseases to hopefully get more research,” said Joseph. “It might not help our daughter, but if it helps somebody’s children in the future, then we’ve done something good.”

While there is no cure for Leigh syndrome, Salem, now 9 months old, has a G-tube for improved nutrition and is on medication to help control seizures. GGC also prescribed a compounded vitamin and supplement mixture that has shown benefits in supporting mitochondrial function to delay the onset and reduce the severity of some symptoms. Unfortunately, the family’s insurance does not cover a pharmacy that can provide this mixture, and Salem’s care team nominated the family for support through the GGC Cares Fund.

The GGC Cares Fund is an initiative of the GGC Foundation that provides financial assistance for genetic testing, care, and treatments for families who are uninsured or underinsured.

“After struggling with the family’s insurance company for several weeks, we made the decision to nominate Salem for the Cares Fund, and within the day they were approved for a full year of coverage for the supplements,” said Alli Davis, a genetic assistant in GGC’s Charleston office who has been assisting the family. “We are now able to fill the prescription with a local pharmacy that is able to ship the medication straight to the family, saving them nearly $4,000 in medical costs.”

“The Cares Fund has provided our daughter with the chance to begin taking the supplements needed so that her mitochondria can have extra help in doing what they naturally should be doing, but can’t,” said Breanna. “Fighting with insurance companies has discouraged us in a way that I cannot describe, but the Cares Fund took that worry away at least for the next year.”

“We are forever thankful and grateful for GGC,” added Breanna. “Everyone has been so nice and understanding, and they are helping our daughter to continue to thrive by being able to take these supplements.”

You can follow Salem’s story on a Facebook page managed by her family.

To support GGC families like the Marras, give to the GGC Cares Fund here or contact the GGC Foundation at (864) 388-1801 to learn more.

Salem’s parents and sisters in “her fight is our fight” t-shirts

 

In 2019, SC Governor Henry McMaster visited GGC to sign Dylan’s Law, legislation that would add Krabbe disease to the state’s newborn screening test, also known as the heel prick test.

The law was named in memory of Dylan Emery, a GGC patient from Ninety Six, SC, who passed away from Krabbe disease at 11 months of age. His family worked with state legislators to add the rare disorder to the SC newborn screening panel allowing future affected infants to receive an early diagnosis with the hope of life-saving treatment. SC began screening for Krabbe disease on May 15, adding it to the panel of 55 other genetic disorders, becoming just the 11th state to test all newborns for this rare condition.

“We have been waiting for this day,” said Dylan’s parents, Matt and Melissa Emery. “This is proof that Dylan’s struggle and suffering will make a difference in other babies’ lives.”

“Because newborn screening is not a diagnostic test, all positive screens from the state must be confirmed to distinguish truly affected infants from false positive cases,” said Francyne Kubaski, PhD, a staff scientist in GGC’s Biochemical Lab. “That’s where GGC comes in.”

Kubaski and her colleagues have been validating the testing of the biomarker psychosine to help with that process. Patients with Krabbe disease are unable to make an enzyme that breaks down psychosine. The buildup of psychosine in the central nervous system leads to the loss of myelin, a protective coating on the nerves, which causes significant neurological impairment.

Patients with Krabbe are typically asymptomatic at birth, but the disease can progress quickly. The infantile form begins with feeding difficulties, muscle weakness/stiffness, and fevers. As the disease progresses, patients may experience seizures, hearing and vision loss, nerve pain, and the inability to swallow and move, with death often occurring within two years.

Treatment for Krabbe disease includes bone marrow or stem cell transplantation which allows the patient to make more of the deficient enzyme, slowing progression of the disease. Once symptoms develop, it’s too late to reverse the damage that has already occurred which is why proponents have advocated adding Krabbe to the newborn screening panel.

Initial screening for all infants born in SC is performed at the state lab through dried blood spots taken from a heel stick. If the state lab identifies a low activity of the Krabbe enzyme, GGC will begin the confirmation process using these dried blood spots to test psychosine levels. By validating the testing using dried blood spots, this confirmatory testing can be performed quickly without obtaining a new sample.

“It is important to include psychosine testing to confirm the diagnosis, as some individuals will display a low enzyme level in lab testing, but in actuality they are producing a sufficient amount enzyme,” said Kubaski. “This is called a pseudodeficiency, and does not cause disease.” But if enzyme levels are low and psychosine is elevated, that is a true positive result. GGC will then follow up with DNA sequencing of the gene responsible for Krabbe disease and patients are referred for consideration of a stem cell or bone marrow transplant.

“For babies identified to have significantly elevated psychosine levels consistent with the infantile form of Krabbe disease, the time from diagnosis to treatment will be critical,” said Neena Champaigne, MD, Clinical Associate Professor and Division Chief of Pediatric Genetics at the Medical University of South Carolina. “The best outcome for survival requires they undergo stem cell transplant before 30 days of life. Coordination of care between the health department, primary care provider, specialists, the GGC laboratory and families will be key.”

Psychosine levels can also be measured on affected infants during treatment to determine if the transplanted stem cells are producing sufficient enzyme to decrease the toxic psychosine.

The Emery family has found comfort in knowing that Dylan’s legacy lives on. “We have always feared Dylan would be forgotten,” they shared. “We feel honored to be the parents of such a brave and amazing soul and are grateful to everyone who loved Dylan and helped put ‘Dylan’s Law’ into motion.”

“It is our hope that lives will be saved and other babies in South Carolina will have a better chance at survival if they are unfortunately diagnosed with this terrible disease,” added the Emerys.

 

Top photo: Matt and Melissa Emery with a photo of Dylan
Bottom photo: Francyne Kubaski, PhD, in GGC’s Biochemical Genetics Lab

Courtney Matheny, PhD, has always had a passion for helping people. She knew from the age of 12, after learning that a friend had a congenital heart defect, that she wanted to make her mark in the world through medicine.

Matheny was originally considering medical school when she went to work in the lab of Drs. Rich and Heather Steet at the University of Georgia. “It didn’t take long for me to absolutely fall in love with using zebrafish to study human disease,” said Matheny, “and within six months of working for the Steets, I decided to apply to graduate school.”

Upon completing her PhD at Emory University, Matheny realized that throughout graduate school she had lost some of her passion because her research wasn’t directly helping anyone. It was then that she reached out to Dr. Heather Flanagan-Steet, who had since moved her zebrafish lab to the Greenwood Genetic Center.

“Even though I didn’t work for her anymore, she was still my mentor,” said Matheny. “She told me about what they were doing at GGC and how I could be a part of it. The compassion I have for others is what truly drives me forward in my scientific career, and rejoining the Steets’ lab at GGC just felt like the right thing for me to do.”

Dr. Matheny joined GGC in 2022 as a postdoctoral associate, or postdoc, in the Center’s Research Division.

A postdoc is a position that many scientists pursue after graduate school to provide additional research experience, skills, and training to further prepare them for a faculty-level career in academia or research.

Dr. Matheny’s current projects involve working with zebrafish in  GGC’s Allin Aquaculture Facility to better understand the causes of neurological symptoms experienced by patients with rare metabolic disorders such as congenital disorders of glycosylation and lysosomal storage disorders.

“I love working with model organisms like the zebrafish because they are such an elegant solution to understanding our own biology and diseases,” said Matheny. “Our goal should be to understand how a mutation affects the whole body and you can only do that by studying the whole organism.”

Matheny’s ongoing postgraduate education will expand this summer. She has been  accepted to participate in the prestigious ‘Zebrafish Development and Genetics’ course at the Marine Biological Laboratory in Woods Hole, Massachusetts. Matheny was one of only 22 individuals selected for the course out of hundreds of applicants. Thorough a rigorous schedule of lectures, bench experiments, and hands-on learning, Matheny hopes to gain a better understanding of the zebrafish central nervous system and new techniques that she can apply to her work at GGC.

“We are extremely excited for Courtney, as this is a tremendous educational and career development opportunity for her,” said Dr. Flanagan-Steet, Director of Functional Studies at GGC. “It will also bring additional visibility to the Center in the zebrafish community – with several world-renowned scientific leaders serving on the course faculty.”

Dr. Matheny hopes this experience will enhance her skills and provide her with the  confidence and expertise to some day run her own research lab. “It feels like I’m at the beginning of a very exciting career and am becoming a true expert in my field of study.” Of her mentors, the  Steets, Courtney said, “Anyone who works with them can tell how passionate they are and how incredibly hard they work to find answers for patients. It’s what I hope someone says about me someday.”

As we took the lights off of our tree in the Diagnostic Lab at GGC this year, we started thinking… ‘What do our genes and holiday lights have in common?’

That’s probably not a question you had ever considered. But, I’ll give you a hint – it has to do with expression.

Even if all the bulbs on every strand of lights are working and connected just right, a Christmas tree cannot express itself or ‘do its job,’ until the switch is flipped and the lights are turned on. Like a perfectly good strand of holiday lights, even our normal genes need to be turned on to do their job.

Wait, what?

Remember in biology class when you learned that all genes have a DNA sequence? For example, a section of DNA may read AAGCTTGCTGTG…. For many genetic conditions, the cause of the symptoms is a typo in that sequence, for example there’s an A where there should be a C. But what if a patient has a gene that is sequenced correctly, but it is simply not turned on? Well, just like a tree that is not plugged in, that gene isn’t expressed. It can’t do its job – which can cause all sorts of problems.

There are many factors that affect gene expression, or when and how genes are turned on and off. This area of study is called epigenetics. Methylation is one way that gene expression is controlled. All of our genes may be sequenced correctly, but when a specific chemical tag, called a methyl group, attaches itself to a gene, it turns it off and prevents it from functioning. This process is often normal. For example, you have genes for eye color present in every cell of your body. However, in the cells of your heart, those eye color proteins are not needed so they are simply switched off.

In other cases, the gene should be expressed, but because of faulty methylation, it isn’t. The gene itself is fine, but it’s not being expressed. In those patients, faulty gene expression can make it look like there is a genetic sequence typo. Patients with clear features of a genetic disorder may find that their sequencing testing is normal. The gene sequence is fine, but it’s simply not being expressed.

So how can you tell if a gene is being expressed like it should?

In 2019, Greenwood Diagnostic Labs at GGC partnered with London Health Science Centre (LHSC) in Ontario to launch a new type of genetic test called EpiSign. EpiSign looks at these chemical tags (methylation) and identifies ‘epigenetic signatures’ that are unique to certain genetic conditions. EpiSign started with the ability to identify 19 conditions, and as we have learned more about epigenetics and identified new signatures for more conditions, it has expanded each year. GGC has completed over 1,000 EpiSign tests, and the most recent version, EpiSign v4, is being launched this week and now includes testing for over 70 genetic conditions – providing patients with answers that were not detectable by traditional methods of genetic testing.

Dr. Bekim Sadikovich of LHSC initially developed the testing process and ability to interpret these epigenetic signatures. In 2016, Dr. Sadikovich partnered with Dr. Charles Schwartz, who was the Director of Research at GGC at that time, to introduce this new technology to GGC. From those early partnerships, Greenwood Diagnostic Labs at GGC along with LHSC and Amsterdam University Medical Centers launched EpiSign in 2019. Greenwood Diagnostic Labs became the first lab in the United States to offer EpiSign to patients, and remains the only US lab providing this testing. In recent years, EpiSign has garnered attention through numerous publications and success stories, and has expanded to labs in the United Kingdom and Australia.

Over the past four years, EpiSign has provided an answer to many families whose diagnosis had been missed by traditional genetic testing technology. Parents have been able to breathe a sigh of relief when their child’s diagnostic odyssey has ended after a journey that, for many, has lasted for years. Clinicians can now give their patients a quick and accurate diagnosis. The question now changes from “What does this patient have?’ to “How are we going to treat them?”

So, when the holiday season rolls around again, pay attention to those lights and remember that when you see Christmas trees ‘doing their job’ this holiday season, think about gene expression and the novel work that is taking place at the Greenwood Genetic Center.

Post by Caroline Pinson, Marketing Specialist for GGC’s Greenwood Diagnostic Labs