Answers for Emily

10.06.20

GGC’s clinicians and researchers team up with international collaborators
to find a long-awaited answer for Emily and her family…

Like most girls her age, Emily Powell, 4, adores her big brother, loves Minnie Mouse, and lights up at the sound of her favorite songs. But Emily is
not a typical 4-year-old. She was born with microcephaly, a condition in which a baby’s head size is smaller than normal.

“We found out about
Emily’s microcephaly from an ultrasound when I was around 28 weeks pregnant,” said her mother, Jaime Powell.

Other symptoms related to congenital microcephaly vary but often include neurological issues, developmental delays, and/or intellectual disability. Causes
can include genetic conditions or exposure to certain viruses or toxins during pregnancy.  

Jaime underwent multiple tests before Emily’s birth to identify a potential cause for Emily’s microcephaly. “All of the tests came back negative, and everything
else looked healthy and typical for a baby at her gestational age. We were told to wait and see.”
 
Emily was born at full term and within a few hours began having seizures. More testing in the NICU failed to reveal a cause. 

Emily
was referred to the Greenwood Genetic Center when she was four months of age, and more genetic testing was initiated. “At the time, we and all her
clinicians were at a loss for the cause of her microcephaly,” said Emily’s father, Dr. Matt Powell. “The team at GGC was upfront with us about the
fact that it would be a stepwise, lengthy process to run the complicated genetics tests.”

After several more genetic tests came up empty, Emily’s geneticist suggested whole exome sequencing which identified a novel variant in a gene known as LMNB1.
This gene encodes lamin B1, a protein that makes up the nuclear envelope, a membrane that surrounds the nucleus of the cell and helps the nucleus maintain
its shape. This variant had not been reported before and other changes in this gene were only known to cause leukodystrophy, an adult-onset neurological
disorder, not congenital microcephaly.
 
“We weren’t sure that this explained Emily’s condition, but as we learned more about this gene’s function, we became hopeful that we may have found an
answer,” shared GGC’s Hannah Moore, MS, CGC, the Powell family’s genetic counselor. Moore
and clinical geneticist, Dr. Steve Skinner, shared Emily’s case with GGC’s research team with
the hope that they could determine the significance of her specific genetic change.
 
Rich Steet, PhD, GGC’s Director of Research, helps oversee the Center’s functional studies initiative
which aims to apply advanced research methods to determine if a newly identified genetic variant, like Emily’s, is actually disease-causing. Steet’s
team reached out to other geneticists and were able to find six other patients from Belgium, Italy, and Spain who also had microcephaly, along with
other symptoms, and had novel variants within this same gene.
 
GGC research technologist, Tonya Moss, led the laboratory efforts by introducing genetic variants from each of these patients into HeLa cells and observing
their effects.
 
The results were clear – when these LMNB1 variants were introduced into the cells, there were obvious abnormalities in the structure and function
of the nuclear envelope. The findings were published in the American Journal of Human Genetics in October.

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

“Knowing the cause of Emily’s microcephaly has allowed us to understand her condition better, and we were also relieved to discover that this mutation
was not inherited,” said Matt. “By confirming this mutation as the cause for Emily’s condition, we can grow our family without the worry of passing
these challenges on to another child.”
 
The Powells have also used their situation to become a resource for other families. Jaime noted that their experience with countless hospitalizations have
helped them be better able to navigate the healthcare system and provide advice for others who must advocate to get what their children need.
 
Matt shared, “We do hope that our participation in this research will raise awareness for this condition, and maybe even inspire more research into a way
to supplement the protein for those with the mutation and possibly improve manifestations of the disease.”

 

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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