to genetic tests. Let's go back to genetic testing. A little bit more discussion about genetic testing. So clinical genetic testing requires certain qualities. Clinical testing requires to be valid and useful. Three required qualities are analytical validity, which whether the test can accurately identify the presence or absence of a specific gene or gene variant. That's really important, I think, because you don't want to be tested by tests that not sure one can even identify the variants, even if it's present. So clinical validity is another thing. How well the genetic variant being analyzed is related to the presence, absence, or risk of a genetic disorder, specific disorder. Clinical utility describes whether the test can provide helpful information about diagnosis, treatment, management, or prevention of a disease. Will the use of the test lead to improved health outcome? So these qualities have to have for genetic tests. And definitely there's some federal standards put in place, health-related testing, including for genetic testing, especially the clear clinical laboratory improvement amendments. There's also a state requirement, especially New York has a stringent requirement for genetic testing, but designed to ensure analytical validity, which makes sure that the tests offered can identify variants when it's there, but may not address clinical validity or clinical utility. However, many of the laboratories have molecular geneticists on staff that they can kind of address those things in the report. And I've seen that often. They're very knowledgeable about how molecular defect relating to clinical features. So there may be some information enclosed in that report, but it may not be regulated by the government. And College of American Pathologists have also a program, Laboratory Accreditation Program, LIP Lab, accredits clinical laboratory to conform to the standards and ensures accredited clinical laboratory to meet the needs of patients and healthcare providers. So this accreditation is really important to clear. I know like laboratories are sent specimens, unknown specimen, and they are supposed to return them with the findings and they have to have certain level of accuracy in detection. So they are tested periodically to conform to the standard. So discrimination is a big deal. Federal legislation enacted in 2008. And I'm really glad that this was enacted, even though this doesn't go far enough for me. It's illegal to request or require genetic information of individual or family members and prohibits the discriminatory use of such information for health insurance and employment. But unfortunately, GINA does not cover life insurance, disability insurance, or long-term care insurance. So there is more to do for us to ensure or protect patients with genetic disorders. And some states have additional protection for the patient with genetic disorder, but not all the test states has that in place. And HIPAA also considered genetic information is protected health information. So prior to 2008, before this act was enacted, I had a patient, about 20 years old patient who came to get the information on breast cancer, BRCA in particular. And her mother was diagnosed with breast cancer and she was just tested with BRCA and she came back positive. But this person who came to us was not even diagnosed with breast cancer or genetic testing. So, you know, there's no reason that anybody should know that she has this condition, but somehow insurance company found out about it from somewhere, from the family history maybe, that all of a sudden she was getting notice of increase in premium on her health insurance or some, she tried to get insurance from several companies and they were giving her either double the premium or some places denied her insurance. So this enactment, GINA was a big deal and I hope that no one gets discriminated against because they have genetic disorders. But, you know, as I said, it does not go far enough. So implications of genetic testing. I already discussed kind of certain issues previously with a calm section, but personal issues of course, like emotional, angry, depressed, anxious, or guilty. Those emotions can be issues when you find out genetic test results. Family issues, tensions, revelation of information about family members. So tensions often happens in a couple too, like when the child has a genetic condition and, you know, the couple may blame each other for the condition, but it's a very, very difficult situation and I've seen many couples divorce because of that. Social issues include like discrimination as I just discussed, even with GINA in place. And financial issues is always, there's additional costs for caring for a patient with a genetic condition and definitely some insurance are not covered by GINA, so they may have to pay higher premium than the others, like life insurance. So limitations, no information about the exact timing of symptom onset. We can provide them with historical information or anything that's available about the condition we can provide them. So they may have some idea, but not the personal information for that particular person, just because we know the genotype. The severity of symptoms cannot be told by knowing the genotype or how symptoms may evolve over time, or how responsive to certain treatment we cannot really know from knowing the genotype. And for many genetic disorders, there's no cure, curative treatment. So that's one of the things very difficult. We can diagnose patients, but we can only provide treatments to a certain point. And there are many research going on to develop curative treatments, but not every research come to fruition to help everybody with genetic condition. So it's very difficult. However, I think there is a benefit to knowing the molecular defects, expanding our understanding of the biology behind the disease in question. So there may be a novel gene discovery, novel pathway discovery, which is really great, especially with the next generation sequencing that I couldn't have imagined to be able to discover novel genes so easily. Enhancing research effort for the disease. And there's also patients build their community of the patient with the same disease so they can help each other, they talk to each other, they kind of give recommendations to each other. So there's some collaborative effort between the patients so that they can help each other and they can give tips, you know, I use this for this, this for that. And especially for patients with children, you know, like the sometimes different formula may work for one child may also work for another child, but those information can be distributed within a group. So they help form different groups for special disorders and they can help each other. So finding the genotype or molecular defect can facilitate development of novel therapies and selection of most suitable or tailored therapies may be possible. So ultimately, implementation of a more individual approach to management is possible, knowing the molecular defect. So I'm all for knowing the molecular defect, but definitely patients need to be in on it. So they need to have informed information step all through the steps of this processes so that they can make the right decision for themselves. We cannot make decisions for them. So let's review the overall points. Clinical genetic tests performed at a clinical laboratory. So definitely at the CLIA laboratory is important because they have their standards. Important to select the most appropriate test, be informed about the type of genetic test being ordered, because if you order a wrong test, if you get negative results, it doesn't mean really anything. Being informed about the gene or gene regions covered by the test. A positive genetic test is informative, but negative genetic result does not confirm negativity. I have mentioned multiple times, but that's a difficult situation. A negative genetic test is only useful for targeted analysis. So family screenings. So program, there is a variant identifying a program and family screening is conducted. And if it comes back negative, that means really this individual does not carry this variant. And that's a sure thing. A variant of unknown significance requires follow-ups for long-term, maybe may take like over 10 years. A need for pre and post genetic tests, genetic counseling is so important so that patients can make informed decisions and be informed about the limitations. Even like getting back the report, genetic report, the laboratory is usually provided with the limitations so you can see where they do not cover. Usually they cover the important portions, but there are portions that some laboratory do not cover. And you should be aware of those limitations and limitations about the genetic tests should be, you know, relate to their, your patients as well. So the patients understand that even, you know, going through a genetic testing, there may be some limits to what we can provide as far as information is concerned, even positive tests.

clinical genetic testing

federal and state standards

Genetic Information Nondiscrimination Act (GINA)

limitations of genetic testing

informed genetic counseling