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

Sandro Rossetti, Elena Bresin, Gabriella Restagno, Angelo Carbonara, Stefano Corrà, Ornella De Prisco, Pier Franco Pignatti, Alberto E. Turco

Research output: Contribution to journalArticle

Abstract

Sixty-seven Italian patients with autosomal dominant polycystic kidney disease (ADPKD) were screened for mutations in the 3' unique region of the PKD1 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 C-terminus tail of the PKD1 protein, polycystin. The mutation also generates a novel Dde1 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 PKD1 chromosome in this family also bears two missense mutations downstream (A12341G and C12384T), not found in the other ADPKD families studied.

Original languageEnglish
Pages (from-to)155-159
Number of pages5
JournalAmerican Journal of Medical Genetics
Volume65
Issue number2
DOIs
Publication statusPublished - Oct 16 1996

Keywords

  • ADPKD
  • heteroduplex analysis
  • mutation detection
  • nonsense mutations
  • PCR
  • PKD1 gene

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)
  • Neuropsychology and Physiological Psychology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this