When Children's Mercy Hospital and Clinics in Kansas City, MO, first started down the road to developing the Center for Pediatric Genomic Medicine in 2011, administrators were originally looking to launch a new carrier test in a CLIA setting.
"They needed a clinical lab director, so I joined the team as a clinical molecular geneticist," explained Carol Saunders, PhD, FACMG, clinical laboratory director of the Center. "It's a great partnership because I, like most lab directors, was interested in using next generation sequencing (NGS) but had no experience with it and limited knowledge. They were unfamiliar with how to run a clinical operation, so we really complement each other's skill sets."
The focus quickly changed to using NGS for diagnostic purposes, instead of carrier screening. "We had such a huge unmet need in our children here at the hospital," Saunders added. "We were the first genome center to be housed within a pediatric hospital, and it has been a wonderful asset to our patients and clinicians."
Diagnosing the Problem
| Stephen Kingsmore, MB, ChB, DSc, FRCPath,
director of the Children's Mercy Center for
Pediatric Genomic Medicine, looks on as
Darrel Dinwiddie, PhD, director of lab operations,
examines a sample. ADVANCE thanks Mark
The Center's specialty is inherited pediatric diseases, and its laboratorians help to ease the frustration of young patients and their families by finding diagnostic answers to their often hard-to-identify illnesses. "We have so many patients who have been through the whole system, year after year getting bounced around different specialties in search of an answer. The financial and psychological toll this takes on families is unbelievable," Saunders stressed. "We have found so many diagnoses for patients that would never have been made by using a gene by gene or small sequencing panel approach because either the gene at fault is a very rare cause of the disease and not on anyone's radar screen, the patients have atypical findings so no one would think to test that gene, or in some cases, the gene has not yet even been linked to a human disease."
The personnel at the Center assist various research departments at Children's Mercy, including Fetal Health, Hematology/Oncology, Neonatology, Pediatrics, Personalized Medicine and Pharmacogenetics, by providing genome, computation and analytic capabilities. Along with genome research, the Center offers exome sequencing, STAT-Seq and the CMH-Dx1 diagnostic test.
While developing the Center, the most important aspect was to develop a team of experts in different groups, such as genomic researchers, bioinformatics and molecular geneticist. "Then we began talking to subspecialists in the hospital about joining the group as coinvestigators, and we have at least one physician from each subspecialty," Saunders said. "These people are the first in the hospital to have access to the Center in terms of enrolling patients in our research studies and to learn about the technology and what it can do (and importantly, what it can't do) for diagnosing their patients."
Changing the Course
Although the sequencing in the Center is done on a research basis, Saunders noted that if they find something definitive, they confirm it in the clinical laboratory and then report it in the medical record. Many of their discoveries have changed treatment plans for patients.
A pair of brothers with early onset inflammatory bowel disease had molecular diagnoses that helped their doctors decide that a bone marrow transplant would be best for their long-term care, reported Saunders. A couple who have had two stillborn babies are pursuing pre-implantation genetic diagnosis for a healthy baby, with the help of a diagnosis from the Center's team. "In addition to research studies, we have been working on validating the 500+ panel for clinical use and have written some very helpful software for analysis and reporting," she added.
For Saunders, working in the field of pediatric genomic medicine is a fun challenge. "Every day, there is something new, and we are all learning so much," she said. "Working on an exome is like doing a puzzle-it's so rewarding when you find the answer. That said, we still have a lot to learn!"
Amanda Koehler (email@example.com) is a freelance writer.
What's in the Lab
Check out the equipment the Center for Pediatric Genomic Medicine uses:
- two Illuminna HiSeq 2000 DNA sequencers (soon to upgrade to HiSeq 2500)
- one Illumina cBot,
- one Illumina MiSeq,
- one Ion Torrent DNA sequencer,
- two custom-designed Perkin Elmer Sciclone G3 liquid handling robots,
- incorporating Agencourt SPRI magnetic bead separation,
- a Perkin-Elmer Janus liquid handling robot,
- a Bio-Rad CFX96 real-time PCR detection system,
- Caliper Lab Chip GX,
- Agilent Bioanalyzer 2000,
- Covaris LE220 96-well plate DNA sonication system, and
- Nanodrop S2000 spectrophotometer.