Christine Eng, MD, Chief Medical Officer at Baylor Genetics, discusses whole genome sequencing and other forms of genetic testing in diagnosing rare diseases.
Transcription:
All of the testing that we do really is designed to address unmet patient and provider needs. As I mentioned, taking new technologies and innovations and adapting them into clinically available solutions, for precision diagnostics. I’m mainly talking about comprehensive options such as whole exome sequencing, whole genome sequencing, and chromosomal microarray. These are comprehensive tests for patients with rare diseases.
As you recall, patients with rare diseases, especially those presenting in the neonatal intensive care unit or at an early age, can have symptoms that are not specific. These symptoms and signs may develop over time, may overlap with many other different disorders. So, the time for diagnosing these patients can get quite lengthy.
Of course, in order to address the patient’s needs, the earliest and quickest diagnosis for medical management and initiation of management, and potentially treatment is critical. Getting a diagnosis fast is the most important thing we can do for a patient. As we know, genetic conditions can be presented a little bit differently. Even if it’s the same condition, it can be slightly different from patient to patient. That’s why having these tests, which are comprehensive, is important to address the needs of rare disease patients.
There is some data in the literature that typically, patients with rare diseases see, on average, about eight different physicians. Four of these may be primary care physicians and four of these may be subspecialists. Over this period of time, which can last anywhere from 5-7 years on average, the amount of resources that are spent in trying to determine what the diagnosis could be is about 19,000 on average in testing alone. Then during this journey, there can be anywhere, on average in the literature, from 2-3 different misdiagnoses along the way.
Whole genome sequencing is, just as the name implies, looking at the entire genome. What I mean by that is it interrogates the genome for a variety of different types of genetic variants. We can look for structural variants, single nucleotide variants, copy number variants, trinucleotide repeats and mitochondrial disorders all in a single test. It gives us the best chance of providing an accurate diagnosis quickly so that patients can be on the path to treatment or more effective management.
This has been a tool that’s been available clinically, I would say, for the past 2-3 years. Prior to that, our laboratory offered it on a research basis through the Undiagnosed Diseases Network of the National Institutes of Health. Our laboratory is the sequencing core for this National Institutes of Health project, which is really looking at patients, rare disease patients, our most challenging patients who have been on the diagnostic odyssey and have been evaluated by multiple physicians without having an answer for their underlying genetic condition. We’ve been the sequencing core for about eight years in this program. We’ve had a broad experience both on a research basis and now on a clinical basis.
In terms of becoming affordable, again, you must look at it from the standpoint of, as I mentioned before, the average $19,000 that a patient has to use to make a diagnosis before these comprehensive strategies were in place. We now know that there are several state Medicaid programs, I believe there are eight currently, that cover whole genome sequencing especially and in the NICU, so rapid whole genome sequencing. Now, there are 15 health plans that cover rapid whole genome sequencing.
I think the field is moving forward and recognizing this in terms of the clinical utility that this test can bring to shorten the diagnostic odyssey. I gave you some examples of whole exome sequencing, but the same can apply for a whole genome sequencing, particularly when there are different kinds of variants that may be responsible for a condition, such as the example I gave where there was trisomy 21, which is chromosomal, and then a single gene defect. Those both can be assessed by whole genome sequencing as opposed to having to have two different tests.
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