Children’s Hospital of Fudan University (CHFU) in Shanghai is widely considered China’s top pediatric hospital. The doctors there see almost 2.5 million patients annually.
One short year ago, WuXi NextCODE and Fudan launched sequence-based rare disease
testing at CHFU using WuXi NextCODE’s RareCODE test and backed by our knowledgebase and the collective expertise of both organizations. In this first year, an astonishing 11,000 patients received sophisticated genomic screening tests to help guide treatment for hard-to-diagnose, or rare, diseases. One-third of those patients got a precise diagnosis, matching the best rates anywhere in the world. In short, Fudan and WuXi NextCODE have, in just one year, effectively launched the field of sequence-based rare disease diagnostics in China and created a program that rivals the largest labs in the U.S.
We had the distinct pleasure of hearing directly from doctors handling these cases and scientists building the database supporting this collaboration at our recent ASHG breakfast, “Using NGS to diagnose rare disease—experiences from three continents.” Dr. Lin Yang, MD, PhD, a clinician at CHFU’s National Children’s Medical Center, presented the hospital’s experience with this rapidly expanding new program.
The service was created thanks to the unique partnership established between the hospital and WuXi NextCODE. WuXi NextCODE contributes its know-how in clinical-grade genomic sequencing, massively scalable informatics, and RareCODE test, backed the most powerful interpretation tools and clinical genetics expertise available.
CHFU, meanwhile, brings to bear the services, knowledge, and skill of its pediatric specialists and the national center of excellence in pediatric medicine housed at the hospital. Notably, CHFU’s Institute for Pediatric Research had previously developed more than 100 tests for single-gene genetic diseases, established multidisciplinary teams of clinical experts to address rare disease, and is among the very first hospitals in China to adopt next-generation sequencing.
Armed with our IT, knowledgebase, and diagnostic tools, this pioneering collaboration has advanced a national center of excellence for diagnosis, treatment, and further medical genetic research. At its core are not just the expertise of both teams, but also a rapidly growing database of mutations causing rare diseases, which the team hopes to grow into the largest in China, and perhaps the world.
Just over 5.5% of babies in China are born with some type of evident syndrome or birth defect. There, as elsewhere, these can impact the skeleton, metabolism, nervous system, circulation, respiration, digestion, and more. These can also be very complex, with multiple phenotypes or overlapping disorders. Some of these are due to causes other than genetics. But a large proportion represent genetic syndromes, of which many are de novo or have never been seen, or at least written about, by other clinical groups.
CHFU started doing single-gene sequencing to help resolve such cases as early as 2010. By 2012 the hospital was also running array CGH, and in 2013 it launched a number of panel tests and an NGS data-analysis pipeline. This history of pioneering genetic analysis put the hospital at the forefront of medical genomics. And things really moved forward fast after CHFU created a joint molecular diagnostic laboratory with WuXi NextCODE.
The two groups confer weekly on difficult cases and, as of now, they have completed some 12,000 genome analyses in just one year, providing a diagnosis in 33% of cases. These include the smallest patients, from the neonatal intensive care unit (NICU)—more than 2,200 of whom received focused exome sequencing and analysis. Just over 13% of those infants received a diagnosis. This lower rate of diagnosis among newborns reflects the greater challenge of working with patients whose signs and symptoms are just appearing. But this number is rising and, as the NICU is a first-tier clinical setting, every diagnosis can be a lifesaver.
Parents and other family member are also often sequenced to determine if the mutations are passed down or have occurred spontaneously (i.e., are de novo). All of that data is incorporated into a database, helping to grow knowledge about the mutations that cause rare diseases.
While there is no specific treatment for most of the syndromes identified, there is an improving picture for a growing number. Patients may receive a lifesaving, or life-changing, treatment plan, or referral to specialists based on their anticipated future needs. Regardless, it is important for the family and doctors to understand as much as possible about what the problem is. It is also helpful for parents and relatives to know that there are potentially pathogenic mutations that run in the family.
At ASHG, our head of communications, Edward Farmer, sat down with Dr. Yang, other scientists and physicians from CHFU, and our CSO, Jeff Gulcher, to talk about the growth of the WuXi NextCODE joint rare disease lab and some of its early successes. I’ll be posting Dr. Farmer’s interview with them here in the days ahead, so be sure to check back and learn more about the launch of rare disease testing in China.