Autosomal dominant polycystic kidney disease (ADPKD) in an Italian family carrying a novel nonsense mutation and two missense changes in exons 44 and 45 of the PKD1 gene
✍ Scribed by Rossetti, Sandro; Bresin, Elena; Restagno, Gabriella; Carbonara, Angelo; Corrà, Stefano; Prisco, Ornella De; Pignatti, Pier Franco; Turco, Alberto E.
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 528 KB
- Volume
- 65
- Category
- Article
- ISSN
- 0148-7299
No coin nor oath required. For personal study only.
✦ Synopsis
Sixty-seven Italian patients with auto-soma1 dominant polycystic kidney disease (ADPKD) were screened for mutations in the 3' unique region of the PKDl gene, using heteroduplex DNA analysis. Novel aberrant bands were detected in 3 patients from the same family. DNA sequencing showed a C to T transition in exon 44 (C12269T), resulting in a premature stop codon (R4020X), predicted to impair the synthesis of the putative intracytoplasmic Cterminus tail of the PKDl protein, polycystin. The mutation also generates a novel DdeI restriction site, and the abnormal restriction pattern was observed both on genomic DNA and on cDNA from the affected relatives, indicating that this is indeed the pathogenetic molecular lesion. Reverse transcriptase-polymerase chain reaction (RT-PCR) performed on lymphocyte mRNA showed that the mutant transcript is normally present and stable. No aberrantly spliced mRNAs were detected. Interestingly, the mutant PKDl chromosome in this family also bears two missense mutations downstream (A12341G and C12384T), not found in the other ADPKD families studied.