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.