J Genet Counsel (2011) 20:327–329 DOI 10.1007/s10897-011-9356-y
CASE PRESENTATION
Self Diagnosis of Lynch Syndrome Using Direct to Consumer Genetic Testing: A Case Study Maegan E. Roberts & Douglas L. Riegert-Johnson & Brittany C. Thomas
Received: 26 July 2010 / Accepted: 8 February 2011 / Published online: 30 March 2011 # National Society of Genetic Counselors, Inc. 2011
Abstract We are reporting what we believe to be the first published case of patient initiated direct to consumer (DTC) genetic testing to test for the presence of a known familial mutation. Our client in this case is from a known MSH2 family; both his/her parent and associated grandparent have previously tested positive for the known familial MSH2 mutation. Using 23andme’s “family inheritance genomewide comparison” option we were able to determine that our client most likely inherited the known familial MSH2 mutation without pursuing single site genetic testing. Our client pursued DTC genetic testing instead of single site genetic testing due to the fear of genetic discrimination. This case shows that patients are still fearful of genetic discrimination, despite the passage of the Genetic Information Nondiscrimination Act (GINA), and that DTC genetic testing may be useful despite the overall negative feeling towards this type of testing in the genetic counseling community. Keywords Direct to consumer genetic testing . Linkage analysis . Genetic counseling . Lynch syndrome . 23andme . InformedDNA
We report what we believe to be the first published case of direct to consumer (DTC) genetic testing used to M. E. Roberts (*) : D. L. Riegert-Johnson Medical Genetics, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL 32224, USA e-mail:
[email protected] B. C. Thomas Molecular Genetics, Mayo Clinic, Rochester, MN, USA
personalize a client’s medical care. To ensure confidentiality, some clinical details are not reported or have been changed. Lynch syndrome is a hereditary cancer syndrome characterized by an increased risk of colon and endometrial cancer (Hampel et al. 2005). The client belongs to a large family affected with Lynch syndrome (LS) in which there is a known mutation in MSH2, one of the Lynch syndrome associated genes. The client was aware that clinical genetic testing for the known MSH2 familial mutation was available and that they were at a 50% risk to have inherited the familial mutation; however, the client was concerned that if they tested positive for the familial MSH2 mutation, and subsequently diagnosed with Lynch syndrome, they would lose or be unable to afford health care insurance. Prior to seeking consultation, our client’s parent and associated grandparent underwent genetic testing for Lynch syndrome due to a family history suggestive of this hereditary cancer predisposition syndrome. This testing revealed the presence of a deleterious familial MSH2 mutation. Shortly before the familial MSH2 testing was performed, our client, our client’s parent and the associated grandparent all submitted sputum samples for genomewide single nucleotide polymorphism (SNP) microarray analysis (23andMe, $499; Mountain View, CA). The family initiated this testing without involvement by a health care professional. The family’s SNP microarray results were available at the time of genetic evaluation, but the client was unable to interpret them. Interpretation of the results by a medical geneticist showed that the client likely carries the familial mutant MSH2 allele without undergoing single site genetic test and without documentation of a positive test result or diagnosis in their medical record (Fig. 1). There are several intriguing aspects of this case; one is the client’s use of DTC genetic testing to perform familial SNP microarray analysis which is similar to
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Roberts, Riegert-Johnson and Thomas
Chromosome 2
MSH2 mutation
MSH2
MSH2 mutation
Chromosome 2
MSH2
Panel A
Panel B
Fig. 1 Panel a, left: The family history with our patient indicated by the arrow. The shaded individuals represent family members who have been affected by Lynch syndrome cancers and have also tested positive for the known familial MSH2 mutation. The chromosome shown is chromosome 2; the arrow indicates the MSH2 locus. The MSH2 locus was identified by entering the name of the gene into a “gene locator” field on the 23andme website. When comparing our patient and their grandparent, it was clear that they share one copy of the shaded area located on the short arm of chromosome 2 (half identical), where MSH2 is located. The only way that our patient and his/her grandparent could be half identical for this region would be if our patient inherited one of his/her grandparent’s MSH2 alleles. The copy of MSH2 inherited from the grandparent must be inherited through our patient’s parent. Since it is known that our patient’s parent and associated grandparent both
harbor the familial MSH2 mutation, our patient is highly suspected to have inherited the mutated MSH2 allele. Panel b, right: A genome wide comparison of our patient and his/her grandparent with Lynch syndrome using the 23andme genome wide customized 600,000 single nucleotide polymorphisms (SNPs) array based on the Illumina 550 with additional SNPs selected from Human Hapmap SNPs. The 23andme array has coverage in the area of the MSH2 locus with 23 SNPs in MSH2 itself. The grey areas represent regions that are half identical and the white areas represent areas where our patient and their grandparent are not. 23andme uses two criteria to classify segments on autosomes as identical by descent. First, the segment must cover an area of at least 5 centiMorgans. Second, there must be at least 700 contiguous shared SNPs. One discordant homozygous call is allowed after every 300 or more contiguous shared SNPs
traditional linkage analysis, one of the most complex techniques in DNA diagnostics (Donahue et al. 1967). The resources the client invested to perform this analysis illustrates the concern some individuals have regarding health care discrimination in the US. Genetic discrimination is, in actual fact, rare, with only a few cases being reported (Slaughter 2008). Even though the Genetic Information Nondiscrimination Act (GINA) was passed on May 21, 2008, many clients are not satisfied with the level of protection this and other state laws offer (Abiola 2008). GINA is a federal law that protects people from discrimination by health insurance companies and employers based on genetic testing results. It is important to note that this law does not cover life insurance, disability insurance or long-term care insurance. The health insurance implications were enacted in May of 2009, while the employer implications were enacted in November of
2009. Health care reforms recently enacted in the US may give further protection. There has been much discussion in the genetic counseling community regarding the efficacy and appropriateness of DTC genetic testing. Genetic counselors are mostly concerned about clients’ understanding of the limitations associated with this type of genetic testing. This case shows that DTC genetic testing may be beneficial when a genetics professional is involved. In June of 2010, 23andMe partnered with Informed Medical Decisions, Inc. (InformedDNA) to provide genetic counseling to individuals undergoing 23andme testing. This service was not an option at the time our client was tested. InformedDNA offers two tiers of service. The first is the “23andMe Personal Genome Service” (PGS) genetic counseling; the genetic counselor providing this service only discusses the client’s SNP microarray results generated
Self Diagnosis of Lynch Syndrome Using DTC Genetic Testing
by 23andMe ($99). The second is “Comprehensive Clinical” genetic counseling; this is a traditional genetic counseling session including evaluation of family history, medical history and recommendations for clinical testing, if determined appropriate ($375). Importantly, InformedDNA does not offer PGS genetic counseling when a client is identified to be a carrier for any of the known disease-causing mutations, rather patients must have the comprehensive clinical genetic counseling. For comprehensive clinical genetic counseling a trained genetic counselor will educate the client about the identified genetic mutation and the implications for them and their family members. Genetic counseling is not mandatory for individuals electing to undergo SNP microarray analysis by 23andMe. This is a service in which the client elects to participate, thus not every individual undergoing SNP microarray analysis by 23andMe found to harbor a disease-causing mutation will undergo the appropriate genetic counseling to understand the associated risks. In the present case, DTC genetic testing offered the client more options than traditional clinical testing; SNP microarray analysis or linkage analysis is not clinically available for Lynch syndrome in the US. Without the client’s use of available DTC SNP microarray analysis, it is unlikely he/she would have had any testing for Lynch syndrome. The suspected diagnosis of Lynch syndrome is clinically impor-
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tant; annual surveillance colonoscopy decreases the lifetime risk of colon cancer in Lynch syndrome by 55%, from an 80% likelihood of occurrence to 25%. Now that there is evidence strongly suggesting the client has a diagnosis of Lynch syndrome, and since the client has met with a genetics professional, he/she is considering clinical genetic testing, via single site analysis, for confirmation and has decided to begin annual surveillance colonoscopy.
Financial Disclosure No financial support. No conflicts of interest.
References Abiola, S. (2008). The genetic information nondiscrimination act of 2008: “first major civil rights bill of the century” bars misuse of genetic test results. The Journal of Law, Medicine & Ethics, 36, 856–860. Donahue, R., Bias, W., Renwick, J., et al. (1967). Probable assignment of the Duffy blood group locus to chromosome 1 in man. Genetics, 61, 949–955. Hampel, H., Stephans, J., Pukkala, E., et al. (2005). Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset. Gastroenterology, 129, 415–421. Slaughter, L. M. (2008). The genetic information nondiscrimination act: why your personal genetics are still vulnerable to discrimination. The Surgical Clinics of North America, 88, 723–738.
