Greenwood Genetic Center - Friends of the Center Newsletter - Winter 2020

Winter 2020

A Newsletter for the Friends of the Center

Internship is Personal Summer student studies disease impacting his family p.

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e r e h W COMPASSION p.

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GGC Foundation Launches 'GGC Cares' Fund

INSPIRES p.

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GGC Contributes to Improving Diversity in Syndrome Recognition

www.GGC.org

PROGRESS p.

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Researchers Rescue Heart Defect in Rare Disease Animal Model

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THE DUKE ENDOWMENT FUNDS 'GENETICS ACCESS FOR ALL'

T he Greenwood Genetic Center (GGC), through the Self Regional

Healthcare Foundation, has been awarded a grant of $899,000 from The Duke Endowment for 'Genetics Access for All,' a project to expand access to genetics services for patients and providers.

"In this current era of genomic medicine, there is an increasing demand for clinical genetics services, but our workforce is insufficient to meet this demand and our current work flows are inefficient," said Mike Lyons, MD, Director of Clinical Services at GGC and lead on the funded project.

"This leads to families facing long waits to be evaluated and tested, and subsequent delays in managing and treating their child's condition."

GGC has provided clinical genetics services since 1974; however, with the increase in demand for services, and inability of genetics training programs to keep up with the ensuing workforce demand, patients often wait for six months or longer to be seen.

"This is not just a GGC issue. Genetics clinics around the country are facing wait times that are as long or longer than ours," said Steve Skinner, MD, GGC Director. "And we have found that as genomic technology has been evolving at such a rapid pace, many non-genetics providers do not feel comfortable ordering and interpreting genetic tests on their own."

'Genetics Access For All' proposes a new standard of genetics care by optimizing access for patients and employing a new system of communication to transform how nongenetics providers engage with genetics providers in order to better manage their patients.

In 2019, GGC and the Medical University of South Carolina (MUSC) signed an affiliation agreement with the goal of improving access to genetic services for patients across SC. One initiative that has grown out of this affiliation is a pilot project with the MUSC Center for Telehealth

to develop an electronic consult (e-consult) system for genetics referrals. The project initially offered the option only to a limited number of referring providers in the MUSC system. Funding from The Duke Endowment will allow that project to expand on a much larger scale.

During the first year of the project, GGC will implement e-consults through an online Dr. Lyons and colleagues at GGC and MUSC have developed an e-consult platform to allow nongenetics providers to upload pilot project which will expand thanks to The Duke Endowment funding. patient information, and receive clinical "We anticipate this project to dramatically impressions and testing recommendations improve wait times for all types of within two business day. E-consults visits, and hope that our success can be will help avoid unnecessary referrals, translated into a new model for genetics improve communication with non-genetic care in clinics nationwide." providers, and enhance efficiency by decreasing the amount of time needed for in-person and telemedicine visits.

In year two, GGC plans to expand the concept to provide electronic patient visits (e-visits) allowing patients to upload their information electronically and quickly receive clinical feedback and recommendations. The goal of e-visits is not to replace in-person or telegenetics visits, but to provide another care option that improves communication with and access for patients.

Lyons says that the ultimate goal of this project is to change the model of genetics care from a long diagnostic odyssey to a more efficient system that decreases unnecessary referrals, expedites diagnoses, and decreases wait times for appointments.

"Through e-consults, we'll be able to more quickly identify patients who need genetic testing and facilitate the appropriate testing," he said. "A rapid diagnosis will allow for more timely and precise management and treatment for all patients impacted by a genetic disorder."

GGC expects to see significant improvements in patient care as the project expands. "Our goals are to complete 50 outpatient and 25 inpatient e-consults and 25 e-visits per month by the end of the grant cycle," said Lyons.

E-consults

How they work

E-consults are an efficient way for non-genetics providers to consult with GGC geneticists to help manage patient care, receive rapid clinical impressions, and if needed, initiate genetic testing with confidence, saving months of delay, worry and uncertainty for their patients. If testing is completed, genetic consultations and counseling will be more focused toward appropriate management and treatment. For example...

Patient seen by primary care provider or non-genetics specialist. Genetic disorder is suspected Provider submits patient information to GGC via secure portal Within 2 days, GGC geneticist/genetic counselor reviews information, offers clinical impressions, and suggests appropriate genetic testing if recommended, non-genetics provider orders testing and schedules genetic visit to review results Test results returned and patient seen by genetics as needed.

Management/treatment plan developed

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GGC CARES FUND The GGC Foundation has always supported the needs of patients and families who need genetics services, but are unable to afford the cost of an evaluation and/or genetic testing.

In 2020, as the need continued to grow, the Foundation formalized a new fund - 'GGC Cares' to specifically meet the needs of these uninsured or underinsured families for whom genetic evaluations and testing may not only provide an answer, but hope for a treatment and better quality of life.

CARES C G G

"GGC's donors are incredible partners in the work we do, and many have expressed a desire to help patient families in a direct way," said Bill Tiller, Executive Director of the GGC Foundation. "The GGC Cares Fund is one way that our supporters can have an immediate impact on a family to help defray the costs of genetic testing, easing one more burden from their minds and allowing them to focus on the needs of their child in what is often a stressful and trying time."

To join us in our commitment to provide compassionate care to all children and families, gifts to the GGC Cares Fund can be made online at www.GGC.org/foundation or by mail. Contact the GGC Foundation for more information at (864) 388-1801.

LEAVING A LEGACY

Family honors sister's memory with gift of hope Dr. and Mrs. Julius L. Leary, Jr., Lynne Leary Lovett, and Kathie Leary Marsh have established the Dianne Patricia Leary Fund for Charcot-Marie-Tooth (CMT) Neuromuscular Disorders at the Greenwood Genetic Center (GGC) with a generous gift to the GGC Foundation in memory of their sister who passed away in April of this year.

Around age two, Dianne began showing symptoms of a neuromuscular disorder, which remained undiagnosed for many years, though clinical features suggested a form of CMT. CMT comprises a varied group of disorders that cause damage to the peripheral nerves that transmit information and signals between the central nervous system and the rest of the body.

There are dozens of genes that can cause CMT, and numerous subtypes have been identified.

GGC was only recently able to confirm Dianne’s diagnosis of CMT by identifying two gene variants using next-generation sequencing technology. Further studies confirmed that these variants were causative for CMT. Dianne was a graduate of Greenwood High School and the University of South Carolina and enjoyed a long career with Duke Energy as a computer analyst in Charlotte where she lived independently until her retirement.

“Dianne’s determined spirit allowed her to live a productive and independent life,” said Dr. Leary. “She influenced and inspired friends, colleagues, and family members with her passion and creativity; her life is an example to everyone how using your gifts can maximize your life’s ambition.”

The Learys' gift will be used to further research into neuromuscular disorders like CMT, including ongoing work to investigate CMT4X. GGC’s clinic space in Greenwood will also be named ‘The Leary Clinic' in Dianne's memory.

“It’s fitting that patients who come to GGC will see Dianne’s name when they enter,” said Dr. Leary. “Her perseverance and drive should serve as an inspiration to all who seek care at GGC to never allow physical limitations to define who you are and what you can achieve.”

“We are humbled to be the recipient of this generous gift to honor Dianne’s life through medical research,” said Steve Skinner, MD, GGC’s Director. “We commit our expertise and the latest technologies available to the better understanding of neuromuscular disorders, including CMT, to ensure that future generations of patients have quick and clear diagnoses and clear paths for treatment.”

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IT'S PERSONAL SUMMER INTERN STUDIES DISEASE THAT IMPACTED HIS FAMILY Gandhi learns how to collect zebrafish eggs for further study at GGC’s Allin Aquaculture Facility.

avi Gandhi, 17, a high school GGC Identifies New K senior from West Chester, PA, already an award-winning Cause of Microcephaly ispatient advocate and foundation executive. This past summer, he

Emily Powell, 4, was born with microcephaly, or a small head.

Testing prior to her birth failed to find an explanation.

Emily was referred to GGC where sequencing identified a novel variant in the gene LMNB1.

LMNB1 encodes a protein in the nuclear envelope that surrounds the cell's nucleus and helps maintain its shape. This variant had not been reported before, and other changes in this gene were not known to cause microcephaly.

“We weren’t sure that this explained Emily’s condition, but as we learned more about this gene, we became hopeful that we may have found an answer,” shared Hannah Moore, MS, CGC, the Powells' genetic counselor. Moore shared the finding with Richard Steet, PhD, GGC's Director of Research, to see if his lab could determine the significance of this variant.

GGC's functional studies initiative uses advanced research methods to determine if a novel variant, like Emily’s, is actually disease-causing. Steet’s team contacted other geneticists and found six more patients in Europe who had both microcephaly and novel variants within LMNB1.

GGC research technologist, Tonya Moss, led the laboratory efforts by introducing the variants from each of these patients into HeLa cells and observing the effects. The results were clear – the LMNB1 variants caused obvious abnormalities in the nuclear envelope.

The findings were published in the American Journal of Human Genetics in October.

“We were pleased to uncover a new genetic cause for microcephaly and share our findings so that other families will be able to reach this diagnosis sooner” said Steet. “Our work is not only providing an answer to families like the Powells, but it is giving them hope that this breakthrough may lead to more discoveries and eventually a therapy.”

Read more at www.ggc.org/the-gene-scene/a

was also an intern in Dr. Richard Steet’s research laboratory at the Greenwood Genetic Center working on a project to identify potential treatment approaches for a rare genetic disorder known as Mucolipidosis II (ML II).

happening so young, I think it’s really heightened my compassion for other people and trying to recognize where they’re coming from," said Gandhi. "For me, the foundation is a way to transform the grief I felt with my brother into really honoring his memory and preserving that.”

Gandhi began his official role with his family’s foundation as Development and Communications Coordinator Gandhi’s accomplishments and drive have been directly influenced at age 13. Since that time, he has taken on primary leadership for

by ML II. His older brother by most of the Foundation’s activities two-and-a-half years, Yash, was including fundraising events, diagnosed with the ultra-rare social media engagement, and genetic disorder at just 11 months connecting families and scientists. of age.

To date, Kavi has spearheaded nearly $500,000 in fundraising ML II is a hereditary metabolic efforts directed to researchers, like condition that causes difficulty in walking, life-threatening respiratory Steet, who are working on a cure for ML II. infections, joint stiffness, and abnormalities of the heart.

At just 15, Kavi's passion and dedication to the ML II Yash passed away just shy of his community earned him the 9th birthday, and his parents, Ash and Sonal, started the Yash Gandhi prestigious designation as the 2018 Global Genes RARE Foundation, vowing to fight this Champion of Hope. disease so that other families would not have to endure such a Kavi spent the early days of his devastating loss. seven-week internship at GGC studying the history and early “Losing my sibling was probably research on ML II. He also worked one of the most formative directly with faculty and staff in experiences for me, and it

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GGC’s Research Division to gain hands-on experience with the use of cell and animal-based models to study the disease process with a focus on GGC's use of zebrafish as a model organism for ML II. He wrapped up his GGC experience with a study of the current research into proposed therapies for this disorder.

“I first met Kavi and his family in 2017 when I attended the Yash Gandhi Foundation’s fundraiser in Pennsylvania,” shared Steet, whose laboratory has received funding from the Foundation for the past five years, including a recent $65,000 grant that is supporting work to identify genes that, when activated, can modify or correct the cellular abnormalities that are seen in patients with ML II. “I’ve been so impressed with Kavi’s enthusiasm and dedication, and I believe he is poised to be a superstar advocate for rare diseases in the future,” added Steet. “My hope is that

we have now also stoked his interest in pursuing a career in research through this summer experience.”

“I always knew that the support our Foundation gave to researchers like Dr. Steet was important and powerful, but I had no concrete picture of what that meant,” said Gandhi. “Getting to spend time in the GGC labs and witnessing with my own eyes the important and revolutionary work that is being done has been indescribably gratifying.”

Gandhi plans to pursue biology and business in college.

“Seeing how the work I have put into fundraising manifests itself at GGC and knowing that I played a small part in the advances that are being made as we speak makes me very proud," he said.

The Gandhi Family in 2007. Left to right: Kavi, Ash, Sonal, and Yash

Learn more about Kavi's family and his work with the Yash Gandhi Foundation at ygf4icell.org.

Cover photo: Gandhi prepares zebrafish embryos for genetic testing to determine if they carry the ML II mutation.

Researchers Rescue Heart Defect in Animal Model Small molecule restores normal heart development in model organism

A transformational gift to GGC has resulted in yet another scientific breakthrough with potential treatment implications for patients worldwide. In GGC's Hazel and Bill Allin Aquaculture Facility, researchers have successfully used small molecules to restore normal heart and valve development in zebrafish with Mucolipidosis II (ML II), a rare genetic disorder. Progressive heart disease is commonly seen in patients with ML II. Cathepsin proteases, enzymes that degrade proteins in the cell, have been associated with later-onset heart disease including atherosclerosis and cardiac hypertrophy, but their role in congenital heart defects has been unclear. The current study offers new insight into how mislocalization of these enzymes alters early heart development in zebrafish with ML II. By treating the fish with small molecules that inhibit these mislocalized enzymes, normal heart function and structure were restored in these animal models.

“Mutations in GNPTAB, the gene that causes ML II, alter the localization and increase the activity of these enzymes which disrupts heart and valve development,” said Heather Flanagan-Steet, PhD, Director of the Hazel and Bill Allin Aquaculture Facility and Director of Functional Studies at GGC. “By inhibiting this process, normal cardiac development was restored in the zebrafish model.

This finding highlights the potential of small molecules in the treatment of this heart defect and the need for further studies."

Flanagan-Steet expects that the current work with ML II zebrafish will provide the basis to move one step closer to a treatment for ML II and potentially other disorders that include congenital heart defects.

This research was supported by funding from Hazel and Bill Allin, the National MPS Society, ISMRD, the Yash Gandhi Foundation, and the NIH National Institute of General Medical Sciences. The study was published in the journal, JCI Insight, in October.

Images from GGC's confocal microscope show that treatment with the small molecule, odanacatib, restores normal morphology to ML II zebrafish hearts and valves.

Left - Normal zebrafish heart (V=Ventricle, A=Atrium); Center - Abnormal heart in a zebrafish model of ML II; Right - Rescued heart structure in a zebrafish model of ML II after treatment with odanacatib.

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'RACE and PAINT THE HELIX' VIRTUAL EVENTS BENEFIT GGC FOUNDATION

T he GGC Foundation

was gearing up for a big year with the 6th annual 'Race the Helix - Upstate' planned for Greenville in March and a huge celebration of the 10th annual 'Race the Helix- Greenwood' in the fall.

Each year, these community 5K races and one mile walks bring together GGC employees, families served by the Center, local runners, and community members who support the mission of GGC. All proceeds from event registration and sponsorships benefit the GGC Foundation in providing compassionate care and highquality genetics services for families across SC and around the world.

Race the Helix began when the Shenal family of Greenwood planned the first event in 2011 as a way to raise awareness for GGC and show their gratitude for the compassionate care they received when their daughter, Ryleigh, was born with a rare chromosome deletion. In the ensuing ten years, the events have raised well over $100,000 to support GGC's diagnostic testing, research projects, and educational endeavors, and ensure that cost is not a barrier for families who need these vital services.

However, these 2020 gatherings of community friends and supporters of GGC became yet another casualty of the COVID-19 pandemic.

Individuals, families, and sponsors alike, donned their celebratory tie-dyed 10th anniversary Race the Helix t-shirts, sharing their photos and race times on social media.

This year's event also added a successful new peer-to-peer fundraising element with runners and walkers inviting their family and friends to join them in their support of GGC through online giving and social media platforms.

In addition to 'Race the Helix,' the GGC Foundation also launched a new online fundraising event, 'Paint the Helix,' a virtual art auction.

Artists and artisans from both the Greenwood area and around the state donated photographs, paintings, pottery, woodworking, jewelry, and other pieces for sale with all proceeds benefiting the GGC Foundation. Sixty-nine pieces were up for auction and the event raised $5,678 to support the Foundation's newly established 'GGC Cares Fund' which offsets the cost of genetic evaluations and testing for uninsured or underinsured patients (see p. 3).

Both Stevenson and Taylor offered items for the auction. Stevenson has a long-standing passion for abstract painting, and when not at GGC, he spends much of his time at his studio at Wyatt Farms in Greenwood.

Taylor, who retired from GGC in 2008, is a gifted wood turner creating intricate bowls, vases, and ornaments.

Taylor's Butterfly Vase was one of the many popular items in the auction.

Vivid Scenes from Race the Helix

“Anyone who has been on the Greenwood Genetic Center campus has seen the Center’s connection to the arts community,” said Tiller, “From the sculptures flanking the fountain in the center of campus to photographs that brighten the clinic rooms and paintings that welcome visitors, GGC has been a longtime supporter of the arts."

Race the Helix - Upstate was forced to cancel just two weeks ahead of the event, and the Race the Helix team made plans to celebrate the Greenwood event in the fall with a virtual race.

"While it certainly wasn't the party that we had envisioned for the celebration of 10 years, we enjoyed tremendous support from our sponsors, and nearly 300 people participated in the event by signing up and running or walking in their own neighborhoods during the week-long virtual race," said Bill Tiller, Executive Director of the GGC Foundation.

Stevenson's 'After Eighty Series 1' was one of the most sought-after paintings in the auction.

GGC's cofounders, Roger Stevenson, MD and Hal Taylor, PhD, who are both talented artists as well as geneticists, helped foster an artistic culture at the Center making an art auction a natural fit.

Top left: Debbie Wiley and Holly Brown showing off their new t-shirts and terrific times from their 5K Top right: Max and Nylah ham it up for the camera as they enjoy their 'Walk the Helix' Center: Dr. Steve Skinner presents the Shenal family Stephen and Jodi (via FaceTime) with a t-shirt quilt from the past ten years of Race the Helix events.

Bottom: Race the Helix committee members and GGC staff, Fran Annese, Boo Ramage, and Amy Botts masked up to stay safe while holding a drive through t-shirt pickup before race week.

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Genetic Diversity

C

EDUCATION in the time of

linicians rely on characteristic facial features and other physical traits to help them make an accurate clinical diagnosis as well as to determine which genetic tests provide the best chance of achieving a quick and accurate answer. Published papers describing various genetic disorders are a useful tool in assisting clinicians with recognizing these characteristic features.

disorders in diverse populations.

The NIH has developed a free webbased reference tool 'The Atlas of Human Malformation Syndromes in Diverse Populations,' which serves as a resource for clinicians world-wide.

Clinicians are invited, with patient consent, to upload clinical descriptions and photographs of individuals with various genetic disorders from diverse populations around the world.

Historically, most textbooks, case reports, and other journal articles that describe genetic disorders have primarily published images and descriptions of patients of Northern European descent as the standard.

In recent years, these images have also been used to train syndromic facial recognition software programs which assist clinicians with syndrome identification using artificial intelligence technology.

"A systematic collection of genetic disorders showing individuals with different ethnicities and backgrounds is extremely valuable in our expanding world," said Prijoles (pictured above).

"By understanding the different presentations of genetic disorders among populations around the world, as well as the within our own diverse communities here at home, we will be better able to serve our patients."

In 2016, geneticists at the National Institutes of Health (NIH) shared their concern over the lack of diversity seen in these resources, and expressed concern that this bias in syndrome recognition may lead to delays in diagnosis for patients of other ethnic and racial groups and precious time lost in managing associated health and developmental issues.

Over the past three years, several GGC clinicians including EJ Prijoles, MD, Assistant Clinical Geneticist in GGC's Columbia office and Roger Stevenson, MD, GGC Senior Clinical Geneticist and Ravenel Curry Endowed Chair in Genetic Therapeutics, have contributed to an international effort led by Max Muenke, MD and Paul Kruszka, MD of the NIH, to better delineate the features of genetic

The group's first paper, focusing on Down syndrome, was published in 2017 in the American Journal of Medical Genetics, and since then the clinical features for six other conditions, Turner syndrome, Cornelia de Lange syndrome, Williams-Beuren syndrome, Noonan syndrome, Rubinstein-Taybi syndrome and 22q11.2 deletion syndrome, across a variety of ethnic backgrounds have been analyzed and shared.

"The clinical geneticists and counselors at GGC are proud to participate in this ongoing initiative," said Stevenson.

"We are so appreciative to our patient families who have allowed us to share photos and clinical descriptions thereby advancing knowledge of genetic syndromes across all populations."

T

COVID

he Gene Machine and Helix Express mobile science labs were fully booked throughout the 2019-2020 school year, poised to serve a record number of schools and students with hands-on laboratory experiences and career exploration activities. But, like most everything else, the tires came to screeching halt in mid-March when schools across SC were closed due to COVID-19.

With schools closed, the GGC Division of Education quickly moved to offering virtual activities for teachers and students across SC. In April, the team developed engaging student videos, including 'The Genetics of Gingers' and 'DNA with Dillon' in recognition of DNA Day. The annual summer teacher's course was moved to a fully online format with recorded lectures and live Zoom labs including activities on topics such as CRISPR gene editing and antibacterial properties of cleansers. The team was also able to make safety accommodations and hold the annual high school summer camp in person in July-August (see p. 10).

With schools resuming in the fall, GGC instructors have made a few schools trips on the Helix Express into classrooms while observing social distancing and safety protocols. They have also led several live Zoom calls providing students with engaging presentations on a variety of genetics-related topics. Video tours of GGC's diagnostic and research laboratories have also been made available to teachers to share a virtual field trip experience with their students.

To take a video lab tour visit: ggc.org/virtual-educational-offerings Photo above : GGC instructors Dillon Gary and Ashley LaVerdure conduct a Zoom class with students at Ridge View High School in Columbia.

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GGC'S COVID RESPONSE

Like most organizations, GGC has adapted to a 'new normal' under COVID-19 protocols.

The impact of COVID-19 on GGC operations was felt immediately in midMarch as GGC made operational changes to keep our employees, patients, and their families safe from exposure to the novel coronavirus, SARS-CoV-2. As an essential service provider, genetic care and testing for patients had to continue.

All employees who could effectively telecommute moved into home offices, while those whose job functions required them to be present in the lab or office began working adjusted hours and staggered shifts to allow for appropriate social distancing.

With only the briefest pause in consultations, GGC's 3-year-old telegenetics program was quickly put to the test. What, in February, had been a successful program serving approximately 10% of GGC's patient population, in March, became the only available service model for all patients.

"Our clinical team and patient work flows adapted quickly as all patient visits became virtual - from the patient's home to the provider's home office," said Mike Lyons, MD, Director of Clinical Services.

"There was definitely an adjustment period for both our providers and our patients, but we have found that for the majority of patients, virtual visits work very well, allowing us to complete physical examinations and effectively educate and counsel our patients."

Telegenetics vs. in-person visits 500 450 400 350 300 250 200 150 100 50 0

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In-person

Telegenetics appointments accounted for approximately 10% of all visits prior to COVID-19. During April-July, all patients were seen virtually. Since August, with precautions in place, in-person visits have resumed for some patients.

"One major challenge we have faced in our telegenetics program in the past has been in obtaining reimbursement for these services," said Lyons.

With the pandemic, as nearly all outpatient medical care shifted to virtual platforms, insurance providers and other third party payers began to cover these visits.

"With the huge number of telemedicine visits conducted across the US over these past months, vast amounts of data will be generated about the effectiveness and quality of telemedicine services, hopefully leading payers to continue to cover these important services even after the pandemic has faded," said Lyons.

"We also recognize that virtual visits do not work for everyone in every situation," said GGC Director, Steve Skinner, MD. "Some families simply prefer in-person visits, and for others, lack of access to a device such as a smart phone or computer or internet service is a barrier."

In late summer, the Center began to resume some in-person appointments with numerous safety measures in place.

Nazneen Sultana, Biochemical Laboratory technologist, wears a face mask while analyzing a test result.

"All employees, patients, and their family members are screened upon entering our facility, and employees are wearing masks anytime they cannot socially distance," said Skinner. "For our patients and families, face mask or shields are

COVID-19 and DNA

B ecause patients can collect saliva samples at home, they became the primary sample type for diagnostic testing starting in mid-March 2020.

March-October 2020

1,851 saliva kits mailed to patient homes ordered (including DNA 2,862 tests banking to store DNA samples for future testing) 59 different genetic tests ordered including 471 Microarray patient tests 451 Microarray parental tests 111 Whole Exome Sequencing 197 FMR1 - Fragile X syndrome tests

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required for family members and any patients who are able to wear them."

Another challenge that has resulted from nearly all visits going virtual has been the difficulty in collecting samples for genetic testing - samples that would normally be acquired while the patient was in the office for their appointment.

Fortunately, this obstacle was not a new issue for GGC, and a system that is in place for other situations could be scaled for widespread use.

"Often in genetics, to appropriately interpret a patient's results, we need to acquire DNA samples from other family members," said Kellie Walden, Director of Diagnostic Development for GGC's Diagnostic Laboratories. "If the family member lives Julie Rodgers, accession clerk, processes saliva samples arriving at GGC's Diagnostic far away or is simply unable to stop by our Laboratory office, we've been able to send kits for them to collect saliva samples at home and return using saliva samples; however, for most "Our accession team has done an them to us." of our high volume tests including single outstanding job to track down the necessary gene testing, whole exome sequencing, information and make sure that the testing Walden also noted that GGC works with gene panels, and microarray, these samples can be completed in both a timely and both pharmaceutical companies and patient work very well with our established assays," accurate manner," Walden added. She also advocacy groups on testing programs said Walden.

"We have found that when noted that turnaround times for tests have designed to identify rare disease patients collected correctly, the saliva samples not been negatively impacted. around the world. The Center already had typically provide sufficient DNA for many a process in place for sending those kits "I'm extraordinarily proud of every member where they were needed for routine clinical of our complex assays." of the GGC team for stepping up to adjust testing and sponsored programs.

The increased number of saliva samples their regular work schedules, quickly learn collected outside of a provider's office new ways of providing care, and maintain So, in March, when patients were being seen has not been without challenges, such as the high quality services our patients have through their smart phones or laptops, GGC samples arriving unlabeled or with missing come to expect from us," said Skinner. "In providers could have a saliva collection kit paperwork.

However, the clinic and lab spite of the difficulty of the situation, our mailed to the patient's home, along with staff have worked together to improve the employees have shown their dedication and instructions on how to correctly collect the collection instructions and implement a commitment to the patients and families we saliva sample and return it to the lab. process to identify samples with missing serve." information.

"Not all genetic tests can be completed

GGC Adds Mitochondrial DNA Testing

A s the 'powerhouses of the cell,' mitochondria are responsible for providing energy for all cellular functions. Disruptions to this energy supply can lead to a number of variable and heterogeneous disorders that can be difficult to diagnose in the clinic. The features can vary

widely - some affect a single organ, while others involve multiple organ systems. Symptoms can present at any age, and their severity, even within the same family, can range from mild to severe. Because of this variability, genetic testing is critical to making the correct diagnosis and guiding management for patients with a suspected mitochondrial disorder.

Mitochondrial disorders can be caused by changes in one of the 20,000 genes in the nucleus of the cell, but the mitochondria themselves also have their own circular chromosomes containing 37 genes, all of which are essential for normal mitochondrial function. Mitochondrial DNA is inherited from the mother, providing a unique pattern of inheritance in most families. It it is also inherited fairly irregularly, meaning that an individual may inherit a variable number of normal and abnormal mitochondrial genes and those variants may be more prevalent in different tissues in the body. All of these factors lead to the significant variability of mitochondrial disorders and complexity in identifying the correct diagnosis.

In October, GGC's Diagnostic Laboratories added two new tests which detect variants associated with more than 20 different mitochondrial-related conditions. To aid in making these challenging diagnoses, GGC offers a sequencing panel that identifies the 29 most common disease-causing mitochondrial DNA variants, accounting for 80-90% of cases for many disorders, as well as an expanded panel of 93 variants, many of which are associated with more than one clinical diagnosis.

Right: Image from GGC's Genetic Counseling Aids, 7th ed. illustrating the difference between nuclear and mitochondrial DNA

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SUMMER CAMP - IN SESSION!

In late spring, GGC's Division of Education was unsure how to handle planned summer activities, but as COVID-19 cases dipped in SC over the summer, the decision was made to move forward with the annual Junior Genetics Scholars Summer Camp for high school students.

The Division of Education not only was tasked with preparing engaging activities for our campers, but they also worked hard to ensure the health and safety of the students and staff. The one week camp was split into two week long sessions to allow for half of the 14 enrolled students to attend each week.

Students and instructors wore masks and social distancing measures were followed, meaning that instead of working in lab groups, the activities were conducted individually, and the always popular GGC lab tours were conducted by video.

"Our team worked diligently to ensure that our students were both safe and engaged during the two summer camp sessions," said Leta Tribble, PhD, Director of Education. "We found that the students were excited to have an inperson activity after so much virtual learning and a spring and summer full of canceled events."

Photo: Camp participant, Jaslynn Norman, prepares a sample for a lab activity to determine if foods have been genetically modified.

BETTER UNDERSTANDING RARE DISEASE Jessica Cooley Coleman, lab manager in GGC's Molecular Diagnostic Lab, is in the midst of an important doctoral dissertation project to better understand and characterize patients with mutations in the MEF2C gene which causes intellectual disability, absent speech, motor delays, autistic behaviors, and epilepsy. MEF2Crelated disorders share many similarities with other neurodevelopmental disorders, such as Rett syndrome, with which GGC has extensive expertise.

Coleman, who began Clemson University's PhD in Healthcare Genetics program in 2019, has worked with Clemson faculty, GGC colleagues, and Dr. Christopher Cowan at MUSC, who has a mouse model for MEF2C, to create a parent survey to better characterize the features of this rare disorder. She received input from several families she met at the SC Autism and Neurodevelopmental Disorders Consortium meeting in Charleston in 2019, and the survey went live in January.

Seventy-three parents responded to the survey. Coleman is currently completing the data analysis with plans to publish her findings to assist families, clinicians and researchers by providing information to bolster the diagnosis and advance treatment.

"The current literature regarding MEF2C is very limited, which is why a larger scale study is needed to gather additional data and improve the clinical description," said Coleman. "I have been very encouraged by the response rate and engagement of families who are so motivated to advance the understanding of this rare disease."

GASS 1ST GRADUATE OF NEW PROGRAM In 2017, GGC welcomed Dr. Jennifer Gass, the first trainee in a new Medical Genetics Training Program - Laboratory Genetics and Genomics (LGG). The LGG program was created to train postdoctoral fellows in both molecular and cytogenetics laboratory techniques. As technologies have evolved in recent years, the development of tests and interpretation of results often requires expertise in both of these laboratory specialties.

Gass joined GGC after earning a PhD in Molecular Neuroscience from Mayo Clinic College of Medicine in Jacksonville, FL, where she also completed fellowships in neuroscience and clinical genomics. She completed GGC's three-year LGG program in June of 2020 where she studied the implementation and interpretation of both molecular and cytogenetic diagnostic tests, as well as the development and validation of new genetic testing assays for use in clinical settings.

After completing her LGG training at GGC, Gass joined former GGC Cytogenetics Laboratory Director, Dr. Katy Phelan, at Florida Cancer Specialists in Fort Myers, Florida as Associate Director of the Genetics Laboratory.

Greenwood Genetic Center 11

VIRTUAL INNOVATION

for Genetic Counseling Education A s a partner with the University of South Carolina School of Medicine's Genetic Counseling Program, it's a common sight to find one of their trainees present in a GGC clinic. Early in the program, they observe clinical visits, and as they progress in their training, so does their participation in patient encounters, under the watchful eye of one of GGC's board certified genetic counselors.

While direct patient counseling is the most common area of practice for genetic counselors, many are also involved in less traditional areas such as laboratory counseling, industry, or clinical trials.

GGC's Jennifer Stallworth, MS, CGC, spent many years in a more traditional role as a prenatal genetic counselor in GGC's Greenville office. However, in recent years her area of interest has shifted to treatment and clinical research. Stallworth now coordinates treatments for patients with lysosomal storage disorders, and counsels patients involved in clinical trials and specialty clinics for conditions such as Rett syndrome and Fragile X syndrome.

With the rapid advances in technology and research into potential treatments for genetic disorders, there are more disorders than ever with approved therapies or open clinical trials.

"Genetic counselors are increasingly involved in helping their patients through the process of clinical trial participation, but this area of clinical research has not been a focus within most genetic counseling training programs," said Stallworth. "With the complexities of clinical trial participation and case coordination required for these therapies and trials, the skill set of genetic counselors can be very beneficial."

To help ease that training gap, Stallworth came up with the idea to

The first mini rotation class discusses clinical trials on a Zoom call with supervisor, Jennifer Stallworth.

Clockwise from top left: Molly Marra - Boise State University, Stallworth, Enrique Lopez - Rutgers University, and Emily Martin – University of Texas - Houston

develop a mini-rotation for genetic counseling students that focuses on treatment and clinical research.

She received funding from Sanofi Genzyme, a biotechnology company involved in developing therapies for rare diseases, to support this experience aimed at second year genetic counseling students from programs across the US. The first class met in October, and within about two weeks of the announcement, all available slots were filled.

Stallworth's two-week rotation is completely virtual. Students are exposed to the grant process and are able to observe GGC case conferences and treatment meetings. Each student selects a current treatment or clinical trial and completes an independent study of the development and utility of the therapy. They also achieve certification in Human Subject Research and Good Clinical Practice which cover best practices and ethical considerations in medical research.

"I appreciated the ability to do research on a clinical trial of my choosing as a way to understand the clinical trial process, informed consent, risks, benefits, and psychosocial aspects," said Emily Martin, a genetic counseling student at the University of Texas - Houston who was in the first class in October. "I also learned about a less traditional role for genetic counselors that still involves clinical care, but in the context of research."

GGC WELCOMES THREE NEW GENETIC COUNSELORS With a nationwide shortage of genetic counselors, GGC was fortunate to recruit three new counselors to our team in 2020.

These new graduates and classmates from the University of South Carolina (USC) School of Medicine's Genetic Counseling program each completed clinical rotations at GGC during their training. They joined the Center in the height of the pandemic, and have exhibited flexibility and professionalism as they have adapted, along with all of us, to continue to provide excellent patient care.

Ellen Richardson, MS, joined GGC’s Greenwood office in June. She is a University of South Carolina graduate and earned her Master’s in Genetic Counseling from USC School of Medicine.

Ellen provides pediatric and adult genetic counseling in both general genetics and metabolic clinics.

Falecia Thomas MS, joined GGC as a Lab Counselor in June. She is a graduate of the University of North Carolina at Chapel Hill and earned her Master's in Genetic Counseling from USC School of Medicine. Falecia serves as a liaison between the GGC Diagnostic Laboratories and our network of referring physicians, genetic counselors, and other healthcare providers.

Meg Wilkes, MS, CGC joined GGC's Charleston office in July. She is a graduate of Clemson University and earned her Master’s in Genetic Counseling from USC School of Medicine.

Meg provides pediatric and adult genetic counseling and achieved certification by the American Board of Genetic Counseling in August.

The Greenwood Genetic Center is a nonprofit institute organized to provide clinical genetic services, diagnostic laboratory testing, educational programs and materials, and research in the field of medical genetics.

106 Gregor Mendel Circle Greenwood, SC 29646

106 Gregor Mendel Circle Greenwood, SC 29646

www.GGC.org

Tel: 864-941-8100 Toll Free: 888-442-4363