Sari, Stefani Harum and Faradz, Sultana MH and Mundhofir, Farmaditya EP (2014) MUTATION ANALYSIS OF PKD1 GENE IN FAMILIAL POLYCYSTIC KIDNEY DISEASE. Masters thesis, Universitas Diponegoro.

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Abstract

Background: Polycystic kidney disease (PKD) is a genetic disorder. The replacement of normal structure with numerous cysts is potential leading to renal failure. PKD contributed to 2.51% end stage renal disease (ESRD) in Indonesia, but its genetic base has been unknown. The most common form of PKD is autosomal dominant polycystic kidney disease (ADPKD). Mutation in PKD1 gene is found in the most of ADPKD cases (85%). Pre-screening molecular diagnostic step is useful to minimize the complexity of mutation analysis in PKD1 gene.

Methods: DNA samples from 27 patients were collected from 13 index families. Fourty six exons of PKD1 gene were amplified in 59 fragments. qPCR-High Resolution Melting (HRM) analysis was utilized as pre-screening diagnosis steps. Afterwards, variant samples which had aberrant pattern were sequenced.

Results: The clinical evidence of highly suggested familial PKD1 was found in6 (46.1%) families. Clinical diagnosis of PKD had associated to hypertension (p- value: 0.045). The amplification was successfully done in 36(61%) amplicons, the remaining 23(39%) amplicons still need to be optimized. Seven variants were identified, in which four variants previously described in literature (c.1001C>T, c.1140C>T, c.1142G>T, c.12276A>G) and three newly described by this study. The new variants were missense mutation (c.1021G>A and c.1240C>T) and synonymous mutation (c.1161C>T). All new variants were predicted as non pathogenic. Two PKD samples from one family was found to carry variant of c.1001 C>T which predicted as likely pathogenic.

Conclusion: Clinical diagnosis of PKD had associated to hypertension (p-value: 0.045).There were 7 variants of PKD1 gene identified in this study. The identification of pathogenic mutation for PKD1 gene has not been completed yet. Further optimization at qPCR-HRM method and mutation confirmation study in healthy control are needed.

Keywords: PKD1 gene, qPCR-HRM analysis, Indonesia

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