Direct DNA sequencing (DS) presents an avenue for molecular diagnosis; however, the genetic analysis of PKD1 (the primary contributor to most ADPKD cases) is intricate. The 5'- region of the gene exists in multiple highly similar copies on chromosome 16. Currently, the ADPKD community endorses direct sequencing using a Long-Range PCR strategy with specific primers as the preferred approach.
However, conducting isolated sequencing for each gene is time-consuming, expensive, and furnishes limited insights necessary for comprehensive diagnosis and prognosis. Furthermore, it's been observed that the primary disease-causing mutation might interact with other PKD or ciliopathy-related genetic loci, thereby influencing the phenotype and increasing the genetic intricacy of the condition.
Consequently, ADPKD experts stress the importance of simultaneously screening all cystic genes under a unified strategy to achieve a more precise diagnosis, encompassing genes linked to atypical PKD forms. In this context, contemporary methodologies like next-generation sequencing followed by variant validation through DS have emerged as the recommended practice. These methods offer swifter, more cost-effective, and dependable genetic diagnoses for sizable ADPKD cohorts.