Meet Chloe

Chloe’s parents had been concerned about her balance from the time she started walking. Then came strong hand and eye tremors. Through the years, Chloe, now 16, has also experienced seizures and learning delays.

Her family has looked to multiple medical specialists and Chloe has undergone numerous EEGs, blood tests, and genetic testing.

Initial genetic tests were normal, until at 12 years of age, her geneticist, Dr. Mike Lyons of the Greenwood Genetic Center’s (GGC’s) Charleston SC office, suggested whole exome sequencing, which analyzes all 20,000 human genes. In Chloe, this test identified a variant in a gene called NUS1. NUS1 has previously been associated with a condition of intellectual disability and seizures and is a potential contributor to Parkinson’s Disease.

“Chloe’s test results identified a variant in this NUS1 gene, but it was a variant that no one had seen before, so we weren’t sure that it was the answer,” said Lyons. “We reached out to the research team at GGC to help clarify its meaning.”

“This was a gene that we were very interested in studying,” said Rich Steet, PhD, Director of Research at GGC. “We ran experiments on skin cells from Chloe and were also able to find two other patients with NUS1 variants and similar symptoms.”

Studies in skin cells showed that the amount of the typical protein produced by the NUS1 gene was reduced in all three patients. Their skin cells also accumulated excess cholesterol in lysosomes.

The research team also developed zebrafish models that mimicked the NUS1 variants seen in these patients.

“Zebrafish and humans share approximately 70% of the same genes, so we can study the effects of human genetic variants in an animal model,” said Heather Flanagan-Steet, PhD, Director of Functional Studies and Director of the Hazel and Bill Allin Aquaculture Facility at GGC. “Studying how NUS1 variants affected the zebrafish provided powerful information, confirming that these variants in our patients were indeed the cause of their symptoms and allowing us to better understand how these variants cause disease.”

GGC’s zebrafish studies showed that the fish also accumulated cholesterol in their cells and, through a tool called a Zebrabox, scientists were able to analyze behavioral swimming patterns in the fish, akin to the movement symptoms exhibited by the patients.

“When we compared the wild type fish to those with the NUS1 mutations, we found that those with the mutations displayed abnormal swimming behaviors including slower swimming and staying near the edges of the swimming area,” said Flanagan-Steet.

Flanagan-Steet shared that in some cases, they can also identify drugs that may rescue the abnormal features in the fish. They can test these drugs on the fish before considering them for human trials.

“The cholesterol storage in both the patient and zebrafish cells suggested that treatments targeting cholesterol accumulation could be therapeutic,” said Steet. “When we treated the affected zebrafish with the drug, 2-hydroxypropyl-beta-cyclodextrin, the fish showed reduced cholesterol accumulation and significant improvement in swimming behaviors.”

“These studies not only confirmed that this variant was indeed the cause of Chloe’s symptoms, providing a long-awaited answer for her family, but they also gave us the opportunity to better understand this rare diagnosis and consider potential treatments,” said Lyons.

Chloe’s family has found hope through their research participation.

“Our journey so far has been to find the ‘why.’ We felt like once we could determine this, we could better understand what could help Chloe,” said her mother, Jessica. “Our hope now is that these breakthroughs with NUS1 will lead to a solution to improve her health.”

A Rare Beauty

The lobby of the JC Self Research Institute at GGC was transformed into a garden – of sorts.

The art exhibit titled ‘Rare Roses’ consisted of 12 paintings that depict real roses with genetic variations. The series was created by Nicole Shannon, an artist from Greenville. Nicole was inspired by her son, who has a rare genetic disorder, and other individuals with genetic differences.

Quinn, now 4, was born with a myriad of health issues and complications. An ultrasound midway through Nicole’s pregnancy identified the first glimpse that there may be a problem. After Quinn was born, genetic testing was performed and GGC’s diagnostic laboratories identified a translocation between chromosomes 6 and 14 that resulted in the loss of 263 genes.

“Until I had a child with a DNA difference, I didn’t know what it was like for people with genetic differences,” shared Nicole in a presentation that she made about her family and her artwork to GGC employees in 2022.

“I was aware of how pervasive racism, sexism, classism, and religious prejudice are, but I never realized how dismissive people could be of other humans when they have a DNA variation. I’ve experienced many instances where my son has been treated as less than due to his DNA,” she said.

Nicole recounted her family’s experiences from the time of Quinn’s birth where people, even medical professionals, have acted “shocked that I unconditionally love my son and wanted what is best for him. They didn’t see him as my son, my little boy, but as a freak – a mistake of nature.”

That’s when she first encountered Dr. David Everman, a clinical geneticist in GGC’s Greenville office, who met with Nicole and her husband, Brendan, to discuss the genetic testing results.

“Thankfully, we eventually met Dr. Everman, and in a moment, everything changed,” said Nicole. Everman, who retired from GGC in 2021, “was able to bring clarity to what caused Quinn’s challenges. He was calm and shared only what he knew – without making assumptions of what he didn’t know.”

That was a turning point for Quinn’s family. From that point on Nicole and Brendan became fierce advocates for their son – challenging the assumptions being made about his abilities.

After 56 days in the NICU, Quinn went home, just in time for Christmas with his family, without a breathing tube and without a catheter, thanks to persistence and advocacy by his parents.

The family soon travelled to Boston Children’s Hospital where Quinn was accepted into the Center for Complex Care. He was evaluated by 27 specialists over the course of two exhausting weeks. He passed a swallow study and was cleared to eat, and they also initiated physical and occupational therapy.

Since that time, “Quinn has grown and improved in so many ways,” Nicole said. “When we think back on what Dr. Everman told us – this was the possibility, this was the hope.”

Nicole Shannon with Rare Rose paintingNicole’s experiences, and her unconditional love of her son, inspired her to find a way, through art, to express that every human is valuable and beautiful, regardless of their DNA.

She chose the rose, a symbol of beauty, because “roses are revered in almost every culture, and as living things, I was sure they must have genetic variation.”

Nicole reached out to botanists all over the world who shared images of roses that have genetic differences. “I was amazed by the photos and knew immediately that I needed to paint them.”

Nicole painted twelve flowers with two different types of genetic alterations – the double flower and phyllody.

Five of the paintings are double flowers where the central reproductive organs of the flower are replaced by additional petals. The flowers appear fuller, and for this reason, many of the roses that are sold in floral shops and grocery stores actually have this genetic alteration.

The other seven paintings reflect phyllody, a genetic change that causes the reproductive organs of the flower to be replaced by leaf-like structures (as in ‘Rare Rose 11’ pictured right).

“Each painting shows that we are all uniquely beautiful and deserving of love,” Nicole added.

“I can say without a doubt that Quinn would not be where he is today had the Greenwood Genetic Center not armed us with the knowledge and support we needed to help Quinn thrive.”

“Dr. Everman provided calm, clarity, kindness, and support when everyone around us seemed overly anxious, emotional, and fearful,” she added. “He undoubtedly changed the course of Quinn’s care and with it, his life.”

Learn more about Nicole and her Rare Roses series at nicoleshannon.com. You can also follow Quinn’s progress on Instagram @OurMightyQuinn.

Meet Jeremiah

Play peek-a-boo with Jeremiah Licorish of Florence, and you’ll be rewarded with a huge grin that lights up both his and his mother’s faces.

But this family has been through the unthinkable in his first year of life, with very few reasons to smile.

At first things were going well. Jeremiah was a happy, healthy newborn, doted on by his mother, Aneesa, and his three big brothers. But when Jeremiah was around 5 months old, Aneesa noticed changes in her youngest son’s development that worried her.

“He started to get weaker,” she shared. “He went from holding his head up to being more slumped and not having any neck control. He stopped reaching for things and wasn’t interested in eating – taking only two ounces of milk.”

His pediatrician wasn’t initially alarmed, thinking he was just being a lazy baby, but Aneesa knew some-thing wasn’t right. She began advocating for her son, first getting an appointment with McLeod Pediatric Rehab for physical therapy. “As soon as we got there, they said he needed more than physical therapy. He needed to see a neurologist and geneticist as soon as possible.”

Aneesa reached out to GGC through the Center’s website and received a call the next morning from Shannon Bell, Telemedicine and Genetic Services Coordinator in GGC’s Florence office. A typical appointment can take weeks or even months and for some families requires travel, but Bell was able to get Jeremiah scheduled with a telegenetics appointment close to home for the next day.

“Through telegenetics, we met Dr. Clarkson who examined every inch of Jeremiah – from how his arms were not moving, to his floppiness, and even his little webbed toes,” recalled Aneesa.

Katie Clarkson, MD, is a GGC clinical geneticist who provides telegenetics consultations for patients from her office in Pennsylvania. She considered several tests, but with a long list of possible diagnoses, she suggested whole exome sequencing, a diagnostic test looking for mutations in the coding regions of all 20,000 genes. Because of Jeremiah’s rapid regression, the test that typically takes 10 weeks for a result was fast-tracked by GGC’s Diagnostic Laboratory, and an answer came in fewer than three weeks.

Ray Louie, PhD, Assistant Director of GGC’s Molecular Laboratory, analyzed Jeremiah’s exome results using a new platform involving artificial intelligence (see p. 5), which quickly identified two changes in the TK2 gene. This gene is known to cause mitochondrial DNA depletion syndrome, type 2 also called TK2 deficiency.

TK2 deficiency is a disease that progresses quickly, causing muscle weakness, problems with chewing, swallowing, and breathing, loss of motor skills, and slowed mental development. Seizures and hearing loss can also develop.

Jeremiah is one of only 107 known cases of TK2 deficiency, and he’s the first African-American male to receive this diagnosis.

Bell recalls sharing the test results with the family, “We always dread giving bad news, but Aneesa was so thankful that we listened to her and found out so quickly. Through her tears, she just kept saying ‘thank you’. I couldn’t help but to cry with her.”

Aneesa was devastated with the diagnosis, but recalls that getting the rapid diagnosis “meant everything.”

“With a baby with a progressive disorder, time is of the essence. Getting the results in a timely manner and being able to connect to resources can literally save his life.”

Once the diagnosis set in, and “I stopped crying,” said Aneesa, “I decided to devote the rest of my life to helping with rare diseases.”

She began exhaustive research into this rare diagnosis, finding nothing but grim information online. Then she connected with another TK2 family and was introduced to Dr. Michio Hirano at Columbia University who is conducting a clinical trial on this rare disorder.

By the time a routine whole exome test result would have been reported, Jeremiah had a diagnosis, and he and Aneesa had made the long journey to New York City to enroll in Dr. Hirano’s study.

Aneesa’s hopes for the trial are that “this treatment turns into a cure and opens up avenues to help other people with rare diseases.” Aneesa has also become a strong advocate for families impacted by mitochondrial disorders.

“In Jeremiah’s case, we were able to mobilize the GGC team across the clinical and diagnostic divisions to get to the diagnosis as fast as possible, which was critically important for Jeremiah,” said Clarkson. “With our lab’s ability to expedite the results and through the use of telegenetics, Jeremiah was able to enroll in this trial earlier and with greater hope for an improved outcome.”

Aneesa recalls that during the appointment where the results were disclosed, there was a very determined black bird knocking on the window of the office. Aneesa found significance in what to most would have been a simple annoyance. To her this experience symbolized persistence even when faced with what seems to be an insurmountable barrier. She likened it to “being able to knock on the right door, and never giving up despite the barriers in your way.”

The Shenal Family

Our daughter, Ryleigh, was diagnosed with a rare chromosomal deletion shortly after she was born in 2010. Since we received her diagnosis, the Greenwood Genetic Center has become part of our family. They made certain that we did not feel alone, and they continue to provide ongoing, compassionate care for our child. The impact they have had on our family and others across the globe everyday is immeasurable. We can’t imagine walking this journey without their guidance and support.

Because of the amazing things they have done for us, and the impact their compassion has had on our family, we started Race the Helix. It is a 5K race and 1 mile run/walk to support their mission – to do our part to make their vision of providing treatments and cures for families impacted by genetic conditions a reality. Through Race the Helix, we hope to raise awareness for GGC, rare genetic disorders and families on the same path as ours.

– Stephen and Jodi Shenal, pictured above with their children, Tyler and Ryleigh

The Jones Family

The journey to becoming parents did not start as an easy one for my husband and I. We suffered the heartache of miscarriage and the unimaginable pain of burying our first born child. Our son, sweet 1 lb 1.4 ounce, 12 inches long, teeny, tiny little Joseph “Hamilton” Jones was born with spina bifida, hydrocephalus, and a heart defect. It tore our hearts out leaving the hospital without him, knowing our dreams and hope for the future were shattered. The next time that we would see him would be at a funeral home filled with people who had lived their lives for decades… his life was only a short 2 hours and 40 minutes. My husband and I were left choosing a small white casket, not much larger than the size of a shoebox for him to be buried in.

After things began to settle down, in the fall of 2007, the sweetest nurse visited us in our home. Her name was Jane, and she was with the Greenwood Genetic Center located in the upstate of South Carolina. She had traveled over 4 hours to visit us! She was that day, and still is, passionately committed to providing heartfelt and compassionate care to families affected by genetic disorders. A part of Greenwood Genetic Center’s mission is researching the causes of these disorders, supporting the families that are affected by them, and discovering ways to prevent them from occurring as frequently. The hope is ultimately preventing genetic defects from occurring at all.

The information that was gathered from the research is complex, but the methods in preventing neural tube defects from occurring are simple … Folic Acid. A small pill, a multivitamin, ONLY 400 mcg, that is taken once daily! I began taking the multivitamin after our loss, and also began eating foods that were rich in folate (spinach, broccoli, asparagus, eggs, cereal etc.)

In 2014, seven years after the devastating loss of our son and meeting Nurse Jane Dean, we welcomed our beautiful daughter Brynleigh. She was born as healthy as can be, weighing 7lbs 9 ounces. About a year and a half later, our son Preston was born, also a super healthy little guy, weighing 9lbs 1 ounce! And a year and a half later after Preston’s birth, we welcomed another baby girl, Ellieana, weighing 7 lbs 11 ounces. Today, we have a healthy 3.5 year old, 2 year old, and 9 month old. These sweet, precious miracles are a gift from God.

We are thankful for the research of the Greenwood Genetic Center and the efforts spent towards supporting the families affected by genetic defects and preventing them from occurring in the future. We will be forever grateful for the services that they provide to our community and the compassionate family that we gained in them after such a life shattering loss.

Chris and Alicia Jones. Aynor,SC

Charlie Connor

After a long three-year struggle trying to have children, our son, Charlie, was born on April 18, 2009. He was our miracle, perfect in every way! When Charlie was five days old, our pediatrician called to notify us that one of the numbers form the heel prick test was a bit high. We headed to the hospital that afternoon for more tests.

I will never forget the following day. It was cool and crisp – not a cloud in the sky. The next thing I know, our pediatrician showed up at our door. The tests had confirmed that our son had a very rare metabolic disorder called Isovaleric Acidemia or IVA and we must go straight to the hospital.

Our pediatrician was in direct contact with Dr. Neena Champaigne at the Greenwood Genetic Center, and we met with her the very next day. She explained that Charlie could not process a component of proteins called leucine. Although IVA is a serious metabolic disorder, we were relieved to find out that it could be treated through his diet. We also learned that Charlie was the only child in South Carolina with IVA. Before Dr. Champaigne left the hospital, she told us that through the support of GGC, “we were not alone.”

There are no words to express our family’s thanks and appreciation to the couriers, to the lab technologists, to the doctors, to the nutritionists, to the entire staff of the Greenwood Genetic Center, all of whom give tirelessly of themselves so that we don’t even feel alone. They are “Charlie’s Angels!”
– Brooks Connor

Lucy's Story

When our daughter Lucy had a metabolic crisis at 7 days old, we were shocked and devastated to find out that she was born with a rare genetic disorder (MSUD). Her newborn screening results did not make it back in time to prevent the crisis, and no one at our local hospital was familiar with the disease. They did not know how to treat her. Calls were made to Greenwood Genetic Center to confirm her diagnosis and guide her care. Dr. Champaigne and Ami...

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