Academic Journal
Detection of a novel nonsense mutation and an intragenic polymorphism in the PKD1 gene of a Cypriot family with autosomal dominant polycystic kidney disease
| العنوان: | Detection of a novel nonsense mutation and an intragenic polymorphism in the PKD1 gene of a Cypriot family with autosomal dominant polycystic kidney disease |
|---|---|
| المؤلفون: | Neophytou, Pavlos, Constantinides, Rolandos, Lazarou, Akis, Pierides, Alkis M., Constantinou-Deltas, Constantinos D. |
| المساهمون: | Constantinou-Deltas, Constantinos D. 0000-0001-5549-9169 |
| المصدر: | Human genetics ; https://www.scopus.com/inward/record.uri?eid=2-s2.0-0029791499&doi=10.1007%2fs004390050235&partnerID=40&md5=3dc30de9ede4eba7e12a01d9b6792c76 ; Hum.Genet. |
| سنة النشر: | 1996 |
| المجموعة: | University of Cyprus: Gnosis Institutional Repository / Ιδρυματικό αποθετήριο Πανεπιστημίου Κύπρου "Γνῶσις" |
| مصطلحات موضوعية: | article, human, Humans, controlled study, female, Middle Aged, priority journal, clinical article, kidney polycystic disease, male, gene frequency, gene product, phenotype, human cell, Base Sequence, gene mutation, Molecular Sequence Data, DNA Primers, heterozygosity, Introns, Mutation, polymerase chain reaction, single strand conformation polymorphism, nucleotide sequence, cytoplasm, Point Mutation, extracellular matrix, Polymorphism, Genetic, carboxy terminal sequence |
| الوصف: | 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 mutations in its 3'-end unique portion in Cypriot patients, by using the method of single-strand conformation polymorphism (SSCP). In one large family, we identified a nucleotide substitution at position 12258 of the cDNA ; this substitutes cysteine-4086 by a premature termination codon (C4086X). It has been inherited by every affected family member but not by unaffected members, nor by patients from 13 other Cypriot families. A new polymerase chain reaction (PCR) primer has been designed to engineer a novel DdeI recognition site upon PCR amplification, thereby allowing easy detection of the mutation by PCR-restriction digestion. The premature STOP codon is expected to remove 217 residues from the putative C-terminal intracellular domain of the gene product, polycystin and thus identifies this part as being critical to the production of the disease phenotype, possibly by interfering with the transmission of signals from the extracellular matrix to the cytoplasm. We also describe the identification of the first polymorphism within the encoding region of the gene. It is at alanine 4091, which is encoded by either GCA or GCG. With a heterozygosity of 35%, it should be extremely useful in informative families, especially because the gene lies in all unstable region and is prone to rearrangements. This polymorphism is readily detectable by PCR-restriction digestion with Bsp1286I. ; 98 ; 437 ; 442 ; Cited By :40 |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | http://gnosis.library.ucy.ac.cy/handle/7/53273 |
| DOI: | 10.1007/s004390050235 |
| الاتاحة: | http://gnosis.library.ucy.ac.cy/handle/7/53273 https://doi.org/10.1007/s004390050235 |
| رقم الانضمام: | edsbas.59EC65E9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1007/s004390050235 |
|---|