2023-04-26 13:31:30
During their search for possible new families with Birt-Hogg-Dubé syndrome (BHD), the researchers came across several people from one family who had symptoms strongly reminiscent of BHG – the typical skin abnormalities and in some cases kidney cancer – but no mutation in the folliculin gene (FLCN).
BHD is caused by mutations in the FLCN gene and occurs in about one in 200,000 people. More than 450 patients with BHD have already been diagnosed in the DNA laboratory at Amsterdam UMC.
Patients often have cysts (vesicles) in the lungs with an increased risk of a collapsed lung, various specific skin abnormalities and kidney cancer.
In a second group of patients from a different family line, various symptoms of BHD were also present from a young age, although without kidney cancer, but with striking skin abnormalities, particularly on the ears. There, too, no mutation was found in the FLCN gene.
Cultured renal cell line
Based on the analysis of all coding genes, the so-called exome of the people involved, the researchers found two mutations: in the first disease, a mutation was found in the PRDM10 gene.
In the second family, a locus on chromosome 5 was discovered, in which, among other things, a mutation was demonstrated in the folliculin interacting protein 1-gen (FNIP1-gen).
Subsequently, a causal relationship was demonstrated with laboratory research, and the suspected mutations were exactly simulated in a cultured human kidney cell line, which showed the relationship with the disease.
reassurance
According to the researchers, the discovery of the two new diseases has several important implications. For example, it is important to continue to draw attention to the condition, since the number of patients and families with BHD is still greatly underestimated.
Families can also gain clarity about the cause of the disease that occurs in the family. This can certainly be reassuring in the case of the FNIP1 mutation, say the researchers, because to date there are no indications that there is an increased risk of kidney cancer.
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