Increasing the efficacy of Genetic Testing for BHD Syndrome

Clinical research isn’t something I’ve touched upon massively in this blog, but a new study by Kunogi et al1 in April’s edition of the Journal of Medical Genetics touches upon the need to constantly re-evaluate and introduce new forms of diagnostic techniques.

In the study, 36 Japanese patients presenting with lung cysts of indeterminate cause underwent FLCN mutation analysis using a conventional approach: denaturing high performance liquid chromatography dHPLC analysis followed by direct sequencing of the exon suspected of harbouring the causative mutation. Germline FLCN mutations were identified in 23 patients using this method. When no mutation was identified by dHPLC, a second round of testing was initiated and involved quantifying the copy number of each exon of the FLCN gene using real-time qPCR. Subsequently, 2 of the remaining 13 individuals were shown to have large genomic deletions in FLCN and therefore, BHD Syndrome.

This study establishes that genetic testing of individuals with suspected BHD Syndrome should employ methods that detect large genomic deletions as well as point mutations. This is clinically relevant since BHD Syndrome is currently under diagnosed and any effort to improve on this is needed. Classically, this is achieved by increased public awareness and educating family health practitioners. Often correct clinical management of BHD Syndrome begins with a positive diagnosis through genetic testing and so increasing the efficacy of this process is greatly welcomed.

1.  Kunogi et al. Clinical and genetic spectrum of Birt-Hogg-Dube syndrome patients in whom pneumothorax and/or multiple lung cysts are the presenting feature. J Med Genet. 2010 Apr;47(4):281-7.

4 thoughts on “Increasing the efficacy of Genetic Testing for BHD Syndrome

  1. Duncan, this blog is discussing false negatives when testing for BHD Syndrome. Are there ever problems around false positives? 15 of the 15 members of my family tested have had positive results. Halve of these people are currently asymptomatic.

  2. Hi Karen.

    Theoretically, any assay system, and that includes diagnostic tests, are liable to producing both false positive and negative results. Neither of these are desirable options and so the assay development procedure is designed to iron out and reduce the possibility of such results to an acceptable number (often in terms of an extremely low percentage).

    From my experience of clinical diagnostics in the British health service I know that validation procedures and quality standards are high for molecular diagnostic assays, and that experiments are always repeated with independent samples, alongside the use of internal control systems, to reduce the possibilty of this occurring, or to be able to recognise a false positive or negative result if one does occur.

    My immediate opinion would be to say that a false positive result in 50% of your family was unusually high! We know that the presentation of BHD Syndrome is extremely variable from person to person so without knowing any more details about your affected family I couldnt comment on why someone currently appears to be asymptomatic. Obviously nobody wants to be unneccessarrily burdened with a positive diagnosis but until you know for sure otherwise it shouldnt be assumed to be an incorrect diagnosis. I would ask if it was possible to get a second test done just to confirm the original results – it would be unlikely to get another false positive result a second time around.

  3. After 8 months of taking Accutane, with no improvement, my doctor referred me to a dermotologist in Nashville TN. He immediately suspected BHD by the “lesions” on my face. He took 4 biopsies. The results came back today as negative, but I am concerned that maybe they didn’t take enough tissue? They did a skin shave biopsy. Should that have been sufficient or should a skin punch been used? I am concerned that I have been given a false negative report.

  4. Dear Tracy,

    I’m afraid we cannot give medical advice. However, the only way to conclusively get a diagnosis for BHD is by DNA testing as, although the results of a biopsy can be indicative (or not) of BHD, they are not conclusive either way.

    If you would like more information on gene testing, this can be found on our website here or please do get in touch with us via our email address:

    I hope this helps.

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