Multiplex-STR panels comprehensive for a timely molecular diagnosis of ADPKD

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease caused by either PKD1 or PKD2 mutations that can lead to fatal end-stage renal disease (ESRD). Direct mutation analysis of ADPKD remains complicated and time consuming. Haplotype-based linkage analysis within-pedigree is a straightforward, alternatively molecular method to diagnose ADPKD, especially in some urgent situations. This study aimed to develop a rapid and efficient short tandem repeat (STR)-haplotype analysis for Thai ADPKD families by investigating in 100 unrelated Thai chromosomes for the informativeness of the 10 and 8 STRs located flanking or within PKD1 and PKD2 genes, respectively. The method was based on multiplex fluorescent polymerase chain reaction (MF-PCR) coupled with detection by laser-induced fluorescent capillary electrophoresis (CE). Two highly informative, multiplex STR panels for rapid, inexpensive and comprehensive molecular diagnosis of both PKD1 (‘PKD1A’: 7 Plex STR) and PKD2 (‘PKD2’: 8 Plex STR) were validated and demonstrated the usefulness in ADPKD families with unknown causative mutations who require timely decision for kidney transplantation from the living-related kidney donors or planning for pre-implantation genetic diagnosis (PGD). This study would be beneficial for differential diagnosis among PKD1, PKD2 or related cystic diseases to timely give a genetic counseling, appropriate management and prognosis to the patients’ families, not only Thais but also Asians and other populations.