Publication date: Jul 09, 2019
-We could hear her screaming as soon as the elevator opened,” Lana Legkiy, Tatiana’s mother, there treated Tatiana and started medication that helped her heart pump.
Along the way, researchers would uncover an undiagnosed heart problem in Tatiana’s older sister, provide a new explanation for why Lana lost a prior pregnancy, and shed light on the unexpected ways in which disease-causing mutations can be inherited.
Tatiana; her older sister, Anna; and the lost fetus each received rare mutations in three genes from their parents – two from their father, one from their mother – that together triggered the heart issues.
-Each one of these, it pushes you a little closer to the cliff, until the point you get pushed off the cliff,” said Dr. Wendy Chung, a pediatric geneticist at Columbia University Medical Center, who was not part of the team studying the Legkiy family.
Tatiana in 2009 Courtesy Lana LegkiyTatiana arrived at the hospital over a decade ago, but the scientific quest only culminated recently, when a team of researchers from the Gladstone Institutes and the University of California, San Francisco, published a paper in Science laying out how they had teased apart exactly what was going on.
Their discoveries were only possible because of advances in stem cell and genome editing wizardry that didn’t exist when Tatiana was born, and because of the encounter with a family whose children had all inherited the same confluence of mutations.
If only one of the children had had the heart issues, -you would never recognize that as a genetic cause,” said Dr. Deepak Srivastava, the president of Gladstone and a pediatric cardiologist at UCSF Benioff Children’s Hospital, who was one of the clinicians involved in Tatiana’s care years ago.
In 2014, while searching for disease-influencing variants of genes involved in the development of the heart, the team landed on three in the MKL2, MYH7, and NKX2-5 genes that Andrey and Lana’s three children all had.
MYH7 plays a key role in the contraction of the heart, while the other two genes help choreograph the formation of the heart during development.
The Legkiy family Courtesy Lana Legkiy-Each of these genes, their function is disrupted in a given number of cells, but each one only causes a slight level of disruption,” said Casey Gifford, a Gladstone scientist and the lead author of the paper.
Researchers not involved with the investigation praised the work, noting just how many steps were required – and how long it took – to corroborate the genetic roots of the heart conditions.
|disease||DOID||sickle cell anemia|
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|disease||DOID||left ventricular noncompaction|
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