Clinical utility of whole exome sequencing for genetic diagnosis of autosomal dominant polycystic kidney disease

8^th World Nephrology Conference

August 15-16, 2016 Sao Paulo, Brazil

Hamad Ali, Naser Hussain, Medhat Naim, Mohamed Zayed, Lauren M Seaburg, Christina M Heyer, Fahd Al-Mulla and Peter C Harris

Kuwait University, Kuwait
Mubarak Al-Kabeer Hospital-Ministry of Health, Kuwait
Dasman Diabetes Institute, Kuwait
Mayo Clinic, USA

Posters & Accepted Abstracts: J Nephrol Ther

Abstract :

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is an inherited renal disease characterized by the accumulation of clusters of fluid-filled cysts in the kidneys with reported incidence ranging between 1:400 and 1:1000 worldwide. ADPKD is caused by mutations in two genes; PKD1, which account for around 85% of all reported ADPKD cases and PKD2. Genetic analysis and mutation screening of ADPKD cases are more technically challenging compared to other monogenic diseases as PKD1 lies in a segmentally duplicated region, such that the first 32 exons are replicated 6 times in pseudo genes located in regions 13-16 Mb proximal to the original PKD1 (16p.13.1) and share between 97.6% to 97.8% sequence homology to the PKD1 gene [16-18]. As these pseudo-regions are less amenable to selection pressure they tend to have high mutation rates when compared to the parent gene. These duplicated regions represent a diagnostic challenge for ADPKD as conventional sequencing is not effective in specifically targeting the genuine PKD1 regions. The development of next generation sequencing (NGS) platforms allowed facilitated faster sequencing of a higher DNA throughput at lower cost in comparison to traditional Sanger sequencing which encouraged wider utilization of such technologies in the medical field. In this study, we evaluate the efficiency of Whole Exome Sequencing (WES) in sequencing PKD1 and PKD2 for detecting ADPKD mutations in patients who were clinically evaluated by ultrasonography. Our results highlight the advantages and limitations of WES in ADPKD genetic diagnosis.

Biography :

Email: hamadd@gmail.com