Novel PKD1 deletions and missense variants in a cohort of Hellenic polycystic kidney disease families
Costi, Constantina Eleni
Georgiou, Ioannis A.
Pierides, Alkis M.
Constantinou-Deltas, Constantinos D.
SourceEuropean Journal of Human Genetics
Google Scholar check
MetadataShow full item record
The autosomal dominant form of polycystic kidney disease is a very frequent genetically heterogeneous inherited condition affecting approximately 1: 1000 individuals of the Caucasian population. The main symptom is the formation of fluid-filled cysts in the kidneys, which grow progressively in size and number with age, and leading to end-stage renal failure in approximately 50% of patients by age 60. About 85% of cases are caused by mutations in the PKD1 gene on chromosome 16p13.3, which encodes for polycystin-1, a membranous glycoprotein with 4302 amino acids and multiple domains. Mutation detection is still a challenge owing to various sequence characteristics that prevent easy PCR amplification and sequencing. Here we attempted a systematic screening of part of the duplicated region of the gene in a large cohort of 53 Hellenic families with the use of single-strand conformation polymorphism analysis of exons 16-34. Our analysis revealed eight most probably disease causing mutations, five deletions and three single amino acid substitutions, in the REJ domain of the protein. In one family, a 3-bp and an 8-bp deletion in exons 20 and 21 respectively, were co-inherited on the same PKD1 chromosome, causing disease in the mother and three sons. Interestingly we did not find any termination codon defects, so common in the unique part of the PKD1 gene. In the same cohort we identified 11 polymorphic sequence variants, four of which resulted in amino acid variations. This supports the notion that the PKD1 gene may be prone to mutagenesis, justifying the relatively high prevalence of polycystic kidney disease.
Showing items related by title, author, creator and subject.
Detection of a novel nonsense mutation and an intragenic polymorphism in the PKD1 gene of a Cypriot family with autosomal dominant polycystic kidney disease Neophytou, Pavlos; Constantinides, Rolandos; Lazarou, Akis; Pierides, Alkis M.; Constantinou-Deltas, Constantinos D. (1996)Mutations in the PKD1 gene on the short arm of chromosome 16 account for 85%-90% of polycystic kidney disease patients in the Caucasian population. After the recent characterization of the gene, we started a search for ...
Presymptomatic molecular diagnosis of autosomal dominant polycystic kidney disease using PKD1- and PKD2-linked markers in Cypriot families Constantinou-Deltas, Constantinos D.; Christodoulou, Kyproula; Tjakouri, C.; Pierides, Alkis M. (1996)Autosomal dominant polycystic kidney disease (ADPKD), is a heterogeneous disorder, primarily characterized by the formation of cysts in the kidneys, and the late development in life of progressive chronic kidney failure. ...
Constantinou-Deltas, Constantinos D. (2001)Autosomal dominant polycystic kidney disease (ADPKD) is an inherited nephropathy, usually of late onset (onset between third to seventh decade), primarily characterized by the formation of fluid-filled cysts in the kidneys. ...