Nephrol Dial Transplant (2000) 15: 477-480
© 2000 European Renal Association-European Dialysis and Transplant Association
A novel frameshift mutation (2436insT) produces an immediate stop codon in the autosomal dominant polycystic kidney disease 2 (PKD2) gene
1 Laboratorio de Fisiología y Biología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina, 2 Unidad de Genética Molecular, Hospital Ramón y Cajal, Madrid, Spain, 3 Biología Molecular Diagnóstica SA, Buenos Aires, Argentina and 4 Instituto de Investigaciones Médicas A Lanari, Universidad de Buenos Aires, Argentina
Correspondence and offprint requests to: Rodolfo S. Martin, Instituto de Investigaciones Médicas, Alfredo Lanari, Medical School, University of Buenos Aires, Combatientes de Malvinas 3150, 1427-Buenos Aires, Argentina.
Background. Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder that can be caused by mutations in at least three different genes. Several mutations have been identified in PKD1 and PKD2 genes. Most of the mutations found in PKD2 gene are predicted to cause premature termination of the protein.
Methods. We analysed an Argentinian family characterized previously as PKD2. The PKD2 gene was amplified from genomic DNA using 17 primer pairs and the products were analysed by heteroduplex analysis. PCR products that showed a variation by heteroduplex analysis were sequenced directly. The mutation was confirmed by sequencing relatives. The segregation of the mutation in this family was verified by restriction endonuclease digestion of PCR products obtained from genomic DNA of all family members.
Results and conclusions. Here, we report a novel mutation present in an Argentinian family characterized as PKD2 by linkage analysis. The mutation, shared by all affected members of the family, is a thymidine insertion at position 2436 of the gene, which results in a translation frameshift and creates an immediate stop codon. This mutation is expected to lead to a truncated protein that lacks the interacting domain with the PKD1 gene product. The thymidine insertion abolished a Ddel restriction site, allowing a rapid test for detection of PKD2 carriers in the family.
Keywords: heteroduplex analysis; mutational analysis; polycystic kidney disease type 2
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