Overall, our results showed that the diagnosis of Von Hippel-Lindau syndrome in our country is difficult most probably because of its heterogeneous clinical manifestation and insufficient knowledge on the diagnostic criteria for the disease. From genetic point of view our results add some novel data on the mutation profile of the VHL gene. In order to prove or revise the diagnosis, early genetic testing is strongly recommended in affected patients and their family members to ensure appropriate follow-up and treatment of the malignancies.
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of hamartomas localized in various tissues which can occur in the skin, brain, kidney and other organs. TSC is caused by mutations in the and genes. Here we report the results from the first molecular testing of 16 Bulgarian patients and one Romanian patient in whom we found six novel mutations: four in the 2 gene, of which one is nonsense, two frame shift and one large deletion of 16 exons; and two in the gene, one nonsense and other frame shift. In addition, we detected 10 previously reported mutations; some of which are described only once in the literature. Our data is similar to the previous studies with exception of the larger number of 1 mutations than that reported in the literature data. In total, 40% (4/10) of the mutation in the gene are located in the GTPase-activating protein domain, while 50% (3/6) are in the gene and clustered in exon 15. All the cases represent the typical clinical symptoms and meet the clinical criteria for TSC diagnosis. In 35% of our cases the family history was positive. Our results add novel findings in the genetic heterogeneity and pathogenesis of TSC. The genetic heterogeneity might correlate to the clinical variability among the TSC-affected families, which makes the genetic counselling a real challenge.
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