So genetic counseling definitely is an integral part of facilitating informed decisions. So during the session, you review medical information and family history, and usually pedigree drawing is done, and provide information on pro and con that we just discussed of genetic testing. They should be related to each patient, and determine how likely the patient has a genetic heritable condition, whether genetic tests would be appropriate for cases, who should be offered genetic testing. This is an important point, because sometimes a person will come to you who may not have the condition or who may not have any phenotype, but she or he says, I have a family history of this and this, but she or he would like to be tested genetically, but there's no information available about genotype. So the best person to be tested first would be another family member who is actually affected with a genetic disorder, and hopefully they're talking to each other and then convince one of the parents who is affected to be tested first before this person can be tested. If it comes back positive with the genotype, then you can be tested. You can test this person, but it's not a good idea to test the person who doesn't have any phenotype or not affected by genetic condition. In question, which type of genetic testing is most appropriate? So during the session, you will discuss and see which one is most appropriate for the situation in hand. Obtain informed consent for genetic testing, and then review the genetic test results after they come back, which should be an extensive one to try, you know, in cases like positive may be easier than negative or uncertain significant findings, but make sure that patients understand what the result entails, and then make plans for follow-ups and referrals, because you may need to ask a subspecialist for follow-up examination for the patient. So genetic test results, each laboratory has a different form for reporting, so it may be confusing, so that make sure to check the type of testing performed on that report, and also they all usually list limitations, so check the limitations. So make sure to check the target regions they tested, does that correspond with what you wanted to order. Hopefully they, you know, they do what you order, but, you know, there may be mistakes happen that make sure the test, because even if that comes back negative, the target region was incorrect, and of course you get negative results, and that might not be your fault. So make sure you check target region on the report, and specimen type is listed usually blood or buccal swab, and negative means no clinically significant variant detected. So it could be a benign variant, or caveat is no variant is identified with the method or target used. So that's always a problem with a negative testing. Reduces the possibility of having the condition in question, but does not eliminate having it. So that case, there should be a discussion on what to do next. Results positive, a variant is identified. So they usually list the gene name with a Hugo Gene Nomenclature Committee approved gene symbol, and protein change is always noted with the location, and complementary DNA change with the location is noted, and the reference sequence used is noted with a RefSeq accession number. So it may appear like this. You have gene name, disease, protein change, cDNA change, zygocity, motor imperatence, and classifications. So likely pathogenic and pathogenic, those are easy. But for the uncertain significance, but this is understandable because they've only found heterozygous, and this is an autosomal recessive condition. So you have to have some kind of discussion. There may be other genes that they should test, or they should re-evaluate the patients for Fanconi anemia. So uncertain significance, especially with a autosomal recessive disorder, but having the condition, you may need to re-evaluate the case better. And maybe there was also secondary finding that there might be found through the whole exome sequencing and whole genome sequencing, and it may list like this, BRCA, this is for hereditary breast and ovarian cancer syndrome, and the protein change and complementary DNA change are noted, and heterozygous, so it's autosomal dominant and pathogenic, and mother had been tested, I assume, so that inherited from the mother. In this kind of case, if the patient had not known that she was at risk of BRCA positive, then she needs to go for screening, but maybe mother was already had the BR breast cancer, then she might have been aware that she may be a carrier for BRCA1. So variant classification goes from benign, likely benign, uncertain, unlikely, pathogenic, and pathogenic. So clinically pathogenic and likely pathogenic variants are typically treated similarly. So they're basically easier, the variant is the cause or likely the cause of the patient condition. So definitive diagnosis made from the clinical diagnosis. Benign and likely benign variants are unlikely the cause of the patient condition, so they are considered as negative results, clinically non-significant. So what do you do in that kind of case? Do we not check the right target, or is there more genes that are out there that cause of this condition? So you may need to think about a little more in this kind of case. So variants of uncertain significant is very common, not enough information is available to categorize them, so you're not able to say either likely benign or likely pathogenic. And classification can change over time, so VUS should not be used for clinical decision making at this moment, but then reclassifying VUS requires continued monitoring for reclassification to either benign or pathogenic. So it may take over 10 years for reclassifying, so periodically you may need to check, hopefully the patient follows up with you afterwards, and then periodically you check the variant if the categorization have changed. It may require international efforts because some of the rare diseases, there may be only a few patients within US, so you may need to go overseas trying to see if there are any patients out overseas with the same genotype, and hopefully find out their phenotype and see if that correlates with patient's phenotype. So ACMG puts out the guideline for how to classify variants, and it tells to look at the population data, computational data, functional data, as well as allelic data, and et cetera. And they give you categories of how to look at variants and provide either supporting, moderate supporting for pathogenicity, strong or very strong supporting, and non-sense mutations are easier because it's usually likely pathogenic, but the missense mutations are more difficult, and you may require to investigate what functional studies may need to be conducted to really decide on the functionality of the protein due to the variant.

Genetic counseling

informed decisions

genetic testing

family history

informed consent