AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE (ADPKD) IN AN ITALIAN FAMILY CARRYING A NOVEL NONSENSE MUTATION AND 2 MISSENSE CHANGES IN EXON-44 AND EXON-45 OF THE PKD1 GENE
S. Rossetti et al., AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE (ADPKD) IN AN ITALIAN FAMILY CARRYING A NOVEL NONSENSE MUTATION AND 2 MISSENSE CHANGES IN EXON-44 AND EXON-45 OF THE PKD1 GENE, American journal of medical genetics, 65(2), 1996, pp. 155-159
Sixty-seven Italian patients with autosomal dominant polycystic kidney
disease (ADPKD) were screened for mutations in the 3' unique region o
f the PKD1 gene, using heteroduplex DNA analysis. Novel aberrant bands
were detected in 3 patients from the same family. DNA sequencing show
ed 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 DdeI restriction site, and the abnorm
al restriction pattern was observed both on genomic DNA and on cDNA fr
om the affected relatives, indicating that this is indeed the pathogen
etic molecular lesion. Reverse transcriptase-polymerase chain reaction
(RT-PCR) performed on lymphocyte mRNA showed that the mutant transcri
pt is normally present and stable. No aberrantly spliced mRNAs were de
tected. Interestingly, the mutant PKD1 chromosome in this family also
bears two missense mutations downstream (A12341G and C12384T), not fou
nd in the other ADPKD families studied. (C) 1996 Wiley-Liss, Inc.