• autosomal dominant polycystic kidney disease
• PKD1
• mutation screening

Autosomal dominant polycystic kidney disease is a common disorder, primarily characterised by progressive renal enlargement and cyst formation, leading, in the majority of patients, to end stage renal disease. Cyst formation has also been observed in liver and pancreas. Cerebral artery aneurysm has also been reported.¹

This disorder is genetically heterogeneous, but about 85% of cases are the result of a mutation in the PKD1 gene, located on the short arm of chromosome 16 (16p13.3). This gene spans about 50 kb of genomic DNA, is composed of 46 exons, and the ORF is 13 kb.^2–5

The incidence of PKD1 in the population is about 1/1000 subjects, making it the most common genetic disorder in humans.⁶ However, routine clinical diagnosis by molecular analysis has not been extensively developed. This is because of two main characteristics of the gene. Firstly, the coding region is large and spans 46 exons. The second and main reason is that sequences homologous to 70% of the coding region are present as nearly identical transcribed copies located closer to the centromere on the short arm of chromosome 16.^7,8 Some of these sequences are transcribed.² This situation has led, until recently, to identification of mutations in only 30% of the non-repeated part of the coding region. Previously, authors have reported RT-PCR based mutation detection, but they only screened the PKD1 gene from exon 16 to exon 46. Recently, two papers have reported different screening strategies for mutation detection in the repeated region of PKD1.^9–11 One involves a long range RT-PCR approach (PKD1 is expressed in lymphocytes) designed to amplify a 13 kb RT-PCR product.¹² This can probably not be used as a routine screening test in a hospital setting. The second approach involves PTT tests and sequencing …