Background: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in either of two genes, TSC1 and TSC2. Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in either PKD1 or PKD2. TSC2 lies immediately adjacent to PKD1 and large heterozygous deletions can result in the TSC2/PKD1 contiguous gene syndrome (PKDTS). PKDTS has been identified in patients with TSC and early-onset severe ADPKD. However, genetic diagnosis with conventional methods proved to be difficult because its genetic aberrations are large monoallelic mutations.
Methods: In the study presented here, we used both multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (array-CGH) for four PKDTS patients.
Results: We were able to detect large heterozygous deletions including TSC2 and PKD1 by both of MLPA and array-CGH in all four patients. And in two patients, array-CGH identified relatively large genomic aberrations (RAB26, NTHL1, etc.), that extended outside of TSC2 or PKD1.
Conclusion: The identical results obtained with these two completely different methods show that both constitute highly reliable strategies. Only a few studies have determined the breakpoints of large deletions in this disease and ours is the first to have identified the breakpoints by using array-CGH. We suggest that these methods are not only useful for the diagnosis of PKDTS but also for elucidation of its molecular mechanism.