PKD Molecular Genetic Analysis

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Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by the autosomal dominant transmission of mutations in one of two genes identified thus far: PKD1 (which accounts for about 85% of all cases and encodes for the polycystin-1 protein) and PKD2 (which accounts for about 15% of all cases and encodes for the polycystin-2 protein).

There are some commercially available services which will sequence the entirety of the PKD1 and PKD2 genes to search for mutations in order to help make a diagnosis of APKD in patients who are at risk (e.g., in younger patients born to a parent with ADPKD who therefore has a 50-50 chance of getting the gene but may not manifest a phenotype until they are older). However, such assays only pick up about 60-80% of mutations. This is mostly due to the genetic complexity of the PKD 1 gene: it is extremely large (46 exons), there are nearby pseudogenes with sequences that are highly homologous, and the gene is filled with polymorphisms (making it difficult to deterimine if a given sequence variant is pathogenic or not). However, the identification of specific mutations by genetic sequencing has been valuable in certain instances, such as if a young family member wishes to donate his/her kidney to a parent with ADPKD and wants to find out if they have inherited the family PKD mutation or not.

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