Investigating the genetics of renal disease in neonates
The hereditary link to renal diseases, such as polycystic kidney disease, has long been recognized in the medical community. Fortunately, recent developments in genetic testing have allowed many physicians to incorporate genetic testing into their daily practice.
|Laurel Willig, MD
However, the genetic underpinnings of many renal diseases affecting children remain elusive, likely a result of complex interplay between genes and environment.
Finding the Connections Between Nephrology and Genomics
Laurel K. Willig, MD, Associate Medical Director for the Center for Pediatric Genomic Medicine and Assistant Professor of Pediatrics, University of Missouri-Kansas City School of Medicine, is trying to shed light on some of these relationships at Children’s Mercy. She is researching the unique connection between pediatric nephrology and genomics.
Dr. Willig is interested in utilizing genomic tools to improve clinicians’ diagnostic and prognostic capabilities for kidney diseases that affect neonates and infants.
"My role is to learn more about the genetic complexity of renal disease in critically ill infants and how we translate these findings from research and apply them directly to patient care," Dr. Willig said.
NIH Grant Investigates Faster Ways to Diagnose Genetic Illnesses
One of the tools Dr. Willig is using to diagnose genetic illnesses in a more timely fashion is STAT-Seq, an Illumina technology developed in partnership with Children’s Mercy that can return results in less than 50 hours. She is working with Stephen Kingsmore, MB, BAO, ChB, DSc, FRCPath, Director of the Center for Pediatric Genomic Medicine, to study the potential for genome and exome sequencing to expand and improve newborn health care. This research is funded by a grant from the National Institutes of Health (NIH).
"We will be examining the benefits and risks of using rapid genomic sequencing (STAT-Seq) technology in the NICU,” Dr. Willig said.
Speeding Up Turnaround Time for Genomic Sequencing
The turnaround time for conducting and receiving genomic sequencing test results has been reduced to 50 hours, which is comparable to other newborn screening tests. As a nephrologist, she also will be looking at the impact this test could have on identifying genetic pediatric renal disease promptly.
"There are cases in neonates, such as nephrotic syndrome, where having that information early on could make a significant difference in the patient’s treatment and outcome,” Dr. Willig said.
TaGSCAN Includes Genetic Testing for Nephrology Disorders
Dr. Willig also is using the Targeted Gene Sequencing and Custom Analysis (TaGSCAN) test, a highly sensitive clinical tool developed at Children’s Mercy, to diagnose certain genetic kidney diseases. The screening panel covers the coding region of more than 500 genes known to cause severe diseases with childhood onset.
"I have personally used the TaGSCAN for my own patients," Dr. Willig said. "There are greater than 20 kidney disease genes included on the panel. In some cases, TaGSCAN is the only clinically available test for these genes that is readily available."
Changing the Course of Pediatric Renal Disease
With information from tests such as the STAT-Seq and TaGSCAN, Dr. Willig sees the potential to achieve a better understanding of genetic pediatric renal disease and treatment. She also is using exome sequencing to find a molecular diagnosis in families with children who have renal disease.
The candidates for exome sequencing are similar to those for TaGSCAN, but this research test covers all the coding regions of the genome. Dr. Willig is using it to study specific nephrology cases. With this test, she can examine a patient’s genome for all known disease associations as well as identify potential novel causes of disease. “Because these diseases are very rare, I am interested in talking with other pediatric nephrologists from across the country who may have an interesting case we could investigate,” Dr. Willig said.
"Additional research helps us validate our findings and better understand the genetic reasons for a child’s renal disease.”
Reaching Out to Other Pediatric Nephrologists
Dr. Willig encourages pediatric nephrologists with a case they would like investigated with exome sequencing or who have questions about TaGSCAN.