Identification of missense and synonymous variants in Iranian patients suffering from autosomal dominant polycystic kidn
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RESEARCH ARTICLE
Open Access
Identification of missense and synonymous variants in Iranian patients suffering from autosomal dominant polycystic kidney disease Fatemeh Khadangi1,2, Adam Torkamanzehi1 and Mohammad Amin Kerachian2,3*
Abstract Background: Autosomal dominant polycystic kidney disease (ADPKD), the predominant type of inherited kidney disorder, occurs due to PKD1 and PKD2 gene mutations. ADPKD diagnosis is made primarily by kidney imaging. However, molecular genetic analysis is required to confirm the diagnosis. It is critical to perform a molecular genetic analysis when the imaging diagnosis is uncertain, particularly in simplex cases (i.e. a single occurrence in a family), in people with remarkably mild symptoms, or in individuals with atypical presentations. The main aim of this study is to determine the frequency of PKD1 gene mutations in Iranian patients with ADPKD diagnosis. Methods: Genomic DNA was extracted from blood samples from 22 ADPKD patients, who were referred to the Qaem Hospital in Mashhad, Iran. By using appropriate primers, 16 end exons of PKD1 gene that are regional hotspots, were replicated with PCR. Then, PCR products were subjected to DNA directional Sanger sequencing. Results: The DNA sequencing in the patients has shown that exons 35, 36 and 37 were non- polymorphic, and that most mutations had occurred in exons 44 and 45. In two patients, an exon-intron boundary mutation had occurred in intron 44. Most of the variants were missense and synonymous types. Conclusion: In the present study, we have shown the occurrence of nine novel missense or synonymous variants in PKD1 gene. These data could contribute to an improved diagnostic and genetic counseling in clinical settings. Keywords: Autosomal dominant polycystic kidney disease, PKD1, Mutational analysis, Iranian
Background One of the most prevalent inherited kidney disorders that affects both kidneys is autosomal dominant polycystic kidney disease (ADPKD), which leads to a progressive loss of kidney function and kidney failure [1]. About one to two infants in 1000 live at birth, and approximately 10% of people who undergo dialysis are affected by this * Correspondence: [email protected]; [email protected] 2 Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 3 Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Full list of author information is available at the end of the article
disease [2, 3]. ADPKD occurs in two types including type I and type II, caused by PKD1 and PKD2 mutations, respectively [4, 5]. PKD2 mutation causes end-stage renal disease at an average age of 74 years, which occurs in 10–15% of cases; on the other hand, PKD1 mutation results in endstage renal disease at an average age of 54 years which occurs in 80–90% of total cases of ADPKD. The latter is the more severe form of the disease [1, 3, 5]. Patients having end-stage kidney disease should receive renal replacement therapy (RRT) or dialysis to sta
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