In a new study conducted by researchers at the University of California, Los Angeles, Health Services, a test that scans all genes at the same time to identify the single mutation causing a child’s rare genetic disorder shows great promise. The findings of this study were published in the online edition of the Journal of the American Medical Association.
At one hospital, this test produced a definitive diagnosis in 40% of children with the most complicated and mysterious genetic disorders by sequencing DNA. From where researchers were 20 years ago with just a 5% diagnosis rate, this is a monumental accomplishment.
One particular child suffered from chronic digestive problems and by 10 months, was not crawling or rolling over. This child’s symptoms were ignored by four neurologists and even a battery of tests performed came up inconclusive. Eager to find answers, the parents agreed to have this child become the first patient in UCLA’s new test called exome sequencing.
DNA was collected from both the child and parents. From there, the child’s genome was quickly scanned using a sophisticated sequencing machine, which was then prepared to that of the parents. On the 18th chromosome, a variant was flagged, giving doctors the diagnosis of Pitt-Hopkins Syndrome, a rare genetic disorder that affects only 250 children in the world.
Based on this case, as well as others, the UCLA study makes a persuasive argument that exome sequencing should be used as a routine clinical test to diagnose children with known or suspected rare genetic disorders.
According to Dr. Stan Nelson, author of the study and vice chair of human genetics, as well as professor of pathology and laboratory medicine at David Geffen School of Medicine at UCLA, this is the first study to show that sequencing a child’s genome along with the parents can dramatically improve the ability to achieve a firm diagnosis specific to rare disorders.
Dr. Nelson adds that a genetic cause for conditions affecting 40% of the hundreds of children that came to UCLA for exome sequencing because of intellectual disabilities or developmental delays was discovered.
In this two-year study, Dr. Nelson worked alongside lead author and assistant adjunct professor of pathology, Hane Lee, to sequence and analyze exomes of 814 children who presented baffling symptoms that despite exhaustive imaging, biochemical, and genetic tests remained undiagnosed.
Earlier testing consisted of one gene being studied at a time whereas exome sequencing has the ability to sift through all 37 million base pairs within a person’s 20,000 genes simultaneously. The result is one DNA change responsible for a rare genetic disorder being singled out. This test also focuses on the exome, which is the protein coding portions of genes accountable for just 1% of DNA but roughly 85% of all glitches that cause human disease.
Although it typically takes eight weeks or less to get results, in medically urgent scenarios, doctors can get answers within about 10 days. In addition, the average out-of-pocket fee of $6,640 is often covered with preauthorization by many insurance companies.
Dr. Wayne Grody, director of the UCLA Clinical Genomics Center and professor of pathology, human genetics, and pediatrics at the David Geffen School of Medicine at UCLA and Mattel Children’s Hospital UCLA points out that when it comes to identifying a precise cause of a child’s illness, exome sequencing plays a vital role.
With this test, doctors, as well as families gain an understanding of how the disease developed and what the best treatment options are. However, exome sequencing also prevents unnecessary and costly testing that produces no diagnosis.