Clinical evaluation and mutation analysis in Indonesian autosomal dominant polycystic kidney disease

Background: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common form of hereditary Polycystic Kidney Disease (PKD) in adults. ADPKD is characterized by massive renal cyst expansion leading to renal failure. Mutation of PKD1 is the most prevalent cause of ADPKD (85% cases). This is the first study which provided genotype and phenotype data of Indonesian patients suspected of ADPKD. Aim: To provide data on exon 13-15 PKD1 as the highest prevalence region of PKD1 mutations and its impact on the phenotype. Methods: Fifteen unrelated patients from Kariadi General Hospital, who fulfilled Ravine renal ultrasound criteria for ADPKD and control matched by gender. Nested PCR from long range (LR) PCR was performed to avoid pseudo gene amplification. Results: History of renal disease in the family was found in 60% subjects. All of the patients were hypertension, and almost half of the cases have end stage renal failure. Two novel variants in PKD1, c.3148G>T and c.3852C>T in two different families were found. Variant c.3148G>T leads to a premature stop: [p.Glu1050*] and was found in the patient and his brother. Variant c.3852C>T is a silent mutation, but software analysis revealed a chance of exon skipping. Conclusions: Hypertension and renal failure is frequent symptom in ADPKD. Pathogenic novel nonsense variant c.3148G>T and a synonymous variant c.3852C>T was found in two different families. Further analysis of synonymous variants for possible effect on splicing should be done on the mRNA level.