The BHD (Birt-Hogg-Dubé) Syndrome DNA project is open to BHD patients and their blood relatives. BHD is caused by mutations in the folliculin [FLCN] gene. (For more details, see www.bhdsyndrome.org/for-families.) Although BHD is very rare, with only about 500 affected families in the world known so far, over 100 different pathogenic FLCN mutations (and about 40 different nonpathogenic ones) have been found. It is common for patients, after their very own personal mutation has been identified, to wonder which ancestors passed the mutation down to them, and whether there are other families in the BHD community who inherited the same mutation from the same distant ancestors. Clearly two people with mutations at two different sites in the gene did not inherit their mutations from the same ancestor, but what about two people with identical mutations? The main goal of the BHD syndrome DNA project is to provide a way to discover which patients are related to each other. Relatedness is shown by two people having a long stretch of matching DNA in the region of the FLCN gene, detectable with FTDNA's Family Finder test.

Once two people find that they have both inherited the same gene from a (probably unknown) shared ancestor (termed the Most Recent Common Ancestor, MRCA), they can compare their known family trees to try to find any ancestors both have in common. Identifying the MRCA, the earliest identifiable carrier of that particular FLCN mutation, is a secondary goal. Success with this step requires either detailed, well fleshed-out family trees for both matches, or, failing that, a fair amount of luck.

If shared ancestors are found, this info may help identify other descendants who have inherited the mutant FLCN allele (an allele is a specific variant of a gene), but have not yet been officially diagnosed with BHD. People with BHD are at risk for developing multiple renal tumors; these can cause death, but are usually controllable if caught early. However, without doing kidney scans the tumors are generally undetectable until they get to an advanced stage. Because of this hidden danger, it may be desirable to find all ancestors predicted to have BHD, then, with further testing, identify which of their descendants inherited the FLCN mutation, and alert them to the need to screen for renal tumors.

Definitive diagnosis of BHD is based on showing the presence of a mutation by sequencing the FLCN DNA. The Family Finder test (technically, a microarray SNV test) does NOT do this. What it can do is identify relatives who share matching segments of DNA --but this knowledge can be surprisingly powerful.

This method of matching patients' DNA in the region of the FLCN gene can be used to trace not only ancestors, but also descendants with the mutation. When a parent has BHD, each child has a 50% chance of inheriting it. When an ancestor (or parent) is known to have the mutation, unless the descendants (or children) show obvious symptoms, it is difficult to know who inherited the mutation and who did not. This project can help. If an affected family meets certain criteria (at least two related, diagnosed cases of BHD who are not siblings or parent & child --these two patients are the positive controls), then any family member who matches both positive controls in the region of the FLCN gene most likely inherited the same mutation, even if no symptoms are apparent. If the family member does not match both positive controls at the location of FLCN, it is most likely that the testee does not have the mutant form of the gene.

For about 10% of families with symptoms that strongly suggest BHD, no mutation can be identified when their FLCN gene is sequenced. Usually these people do have a mutation in FLCN, but it is a type which is easily missed by sequencing. If there are two people in the family (not siblings or parent & child) who have clear symptoms of BHD and can serve as positive controls, this method should still be able to identify which other family members inherited the mutant FLCN allele associated with the symptoms --OR it may show that in this family the symptoms are associated with some gene other than FLCN (a fascinating possibility, but unlikely). In the latter case, if several extended family members with symptoms test with Family Finder, the results may help narrow down the location of this other disease-causing gene in the DNA.

Current status: WE NEED PARTICIPANTS! As yet we have only three families in the project, with mutations c.296delA (previously reported as c.751delA), c.1285delC (previously reported as c.1733delC), and c.1528_1530delGAG (previously reported as c.1983-5delGAG).

How to join the project: You can participate in the project by simply providing me with your information, no test is required. But in FTDNA's terminology, "joining the project" implies two steps: 1) getting your family's information into FTDNA's Family Finder database either by the purchase of an FTDNA Family Finder test, or by importing ("transferring") microarray results from AncestryDNA or from version 3 of 23andMe; and 2) clicking a "join the project" button.  Joining the project not only encourages contact between project participants, but also allows me (the project administrator) to use automated tools to compare test results between all of the project members.
  * If you have already done a Family Finder test, first log in to your FTDNA account, then click here, or click the "Join" button near the top of this Project Background page, and enter your kit # & password again.
  * Transferring (importing) your "raw data" from another company at a big discount - This is possible IF you have already taken certain older, compatible versions of the 23andMe or Ancestry.com test.  For 23andMe, only "version 3" results, tested between November 2010 and November 2013, can be imported to Family Finder.  For Ancestry.com, I think they made their test incompatible with Family Finder in early 2016, but I don't yet know details; autosomal DNA tests taken before the cutoff date can be imported.  As of early 2016, transferring test results cost $39, vs. $79 to buy the Family Finder test. Contact me for info on how to do this.
  * If you want to buy a Family Finder test and do not already have an account with FTDNA, click here or click the "Join" button, scroll way down the page, and follow the link to buy a Family Finder test kit. (If you are interested in any of the other types of DNA tests offered there, I would be glad to provide advice.) A few days after ordering, you will be given an online account where your "kit number" is your ID. After you pay, they will send you a DNA test kit (described here: www.familytreedna.com/learn/using-the-kit/family-tree-dna-test-kit ). You scrape the inside of your cheek with a mini-toothbrush, which collects a small amount of cheek cells from which the DNA will be extracted. You put the cheek scraper into a vial of preservative, seal it, and mail it back to FTDNA. Currently FTDNA says test results will be returned about 8 weeks later.
NOTE this is not a blood test, there is no blood drawing involved, this is done in your own home.

On the other hand, for those who have tested with AncestryDNA or 23andMe (any version, 2, 3, or 4) and don't want to import your data, if you submit your raw DNA results to www.GEDmatch.com , and IF patients with Family Finder results are willing to do the same, your DNA can still be compared to theirs. GEDmatch survives on donations, but they provide this service for free.

If you don't want to purchase a Family Finder test but have had FLCN sequencing, and know the specifics of your mutation (details are usually in the report from the sequencing lab, which you can ask your doctor for), I would appreciate it if you would email me your contact info together with details of your mutation. I can put you in touch with others who contact me and have the same mutation, so you can check whether a family tree connection can be found. My email address is rtx at cox dot net.

I am very conscious of participants' need for privacy.  While I will do my best to keep names and details from being visible to the public, I cannot guarantee privacy. The act of joining a Family Finder project aimed at families of BHD patients is itself a potential loss of privacy --you would be disclosing that someone in your family may have BHD. For that reason, in any public communication where specific project members are mentioned (this will be rare, but conceivable), members will be identified only by a numerical user ID  (their FTDNA kit number), not by name. In contrast, everyone who you match in the Family Finder database will have access to your email address, as well as details and locations (along the chromosomes) of your matching DNA segments. This is to allow matches to contact each other directly, to compare family tree info in order to try to find shared ancestors. Your matches cannot find out about your mutations by simply looking at the details of your match with them  --unless they actually match you in the region of the FLCN gene.  This is extremely rare.  However your matches may be able to see that you are a member of this project.  If you want to be extra careful you could give FTDNA a made-up name for the person being tested, but a valid email address and postal address is required.

PLEASE NOTE - while this kind of comparison is usually extremely reliable when comparing close family members, there are circumstances where a determination using this method (microarray SNV testing) can be incorrect. Definitive diagnosis of BHD is based on showing the presence of a mutation by sequencing the FLCN DNA. The microarray test is not sequencing, and neither I nor Family Tree DNA can be held responsible in any way for errors in determinations based on microarray test results. Medical decisions should NOT be based on these nonclinical microarray test results or participation in this project; medical decisions should not be made until the presence or absence of a mutation is confirmed by sequencing.

The flip side of the caveat above is that IF (esp. in the USA) your insurance company asks if you have ever been tested for a genetic disease (and assuming you have done no other tests for genetic disease), you can honestly answer "No." As powerful as this test is given the proper positive controls, THIS IS NOT AN FDA-APPROVED TEST FOR GENETIC DISEASE. In fact, FTDNA has taken pains NOT to report any SNV results with major medical implications in their raw data.

If a pair of test subjects share an ancestor far enough back in time, this kind of comparison may not show that the pair are matches to each other. (We're not talking Adam & Eve here.)  The accuracy of the prediction depends on the length (in centimorgans, cM) of DNA shown as a match between two people, the match length decreases over time, and it's statistical, with wide variation. 

Matches found in patients from groups known for endogamy (e.g. Ashkenazi Jews, French Canadians, Mennonites) may be less interpretable. It should still work to some degree, but may not detect shared ancestors quite as distant as it will for non-endogamous populations. When this problem exists, FTDNA will usually report an unusually large number of matches from their database in this DNA region.

23andMe.com is a competing product very similar to Family Finder.  Both work, as long as all people to be compared have tested at the same company (i.e. are in the same database.)  The DNA comparison tools at  23andMe may even be easier to use.  However the price per test at 23andMe is now twice what it is for Family Finder.  This can be a big hurdle, and is a consideration if your intent is to test many people within your extended family, in order to determine which of them inherited a mutant allele.  You don't need to be part of a project to test your own family; it can be done using either company as long as everyone in the family tests at the same company.  

On the other hand, if your goal is to try to find others with the same mutation who are not among your known family members, there is no project for this purpose at 23andMe.  (However, you are welcome to work with me.)  At 23andMe there is just no way to know, by looking at your list of matches and before contacting them, whether a person matches you in the region of the FLCN gene or not.  My intent in setting this project up at FTDNA (with their help and tools) is to try to attract more BHD patients and families, in order to enable them to contact and cooperate with each other.

About Ancestry.com's DNA test:  As mentioned above, Ancestry does not have a tool on their site that allows you to look at matches in the regions of specific genes.  (There is a workaround at gedmatch.com.)  Ancestry has changed the testing platform they use, so now it tests almost 70 SNPs within the FLCN gene (in contrast to ~12 or so at other companies).  So there is more chance that your variant can be DIRECTLY identified at ancestry.com.   This may have implications for your cost and coverage for life insurance etc that are not protected in the US by GINA.  Also, the people controlling Congress are trying to limit GINA protections.  So if this is a concern, you may want to AVOID DNA testing at Ancestry.com.  If this is NOT a concern, Ancestry.com has definite advantages, though they are balanced by lack of info on matching over the region of specific genes.

Resources: As mentioned above, www.bhdsyndrome.org is an excellent source of information about BHD. There is a Facebook group for patients and families, www.facebook.com/groups/454615147912181, "a place for those affected by BHD to ask questions, express fears and concerns, share their experiences. You can be the person with BHD or a caregiver or anyone with knowledge of the disease." It is a closed group, which means posts made there are not easily accessible by the general public. A listing of all known FLCN mutations is here.

This web page is very hard to find; I doubt it can even be found using FTDNA's Project Search tools.  So if you want to return to this site, you should probably bookmark it in your browser.  You can use this shortened URL to get back to this page: bit.ly/FTDNA_BHD

About me: I am a volunteer administrator, and receive no compensation from FTDNA. While running a project like this isn't really rocket science, I have a PhD in biophysics from UC Berkeley. I did postdocs in cell physiology at the University of Colorado Health Sciences Center and the University of Oklahoma before starting a career in pharmaceutics.