Investigation of Distribution of PKD1, PKD2 and GANAB Genes in Autosomal Dominant Polycystic Kidney Patients in Turkish Population
Mujgan Ozdemir Erdogan1*, Başak Gogus1, Handan Yildiz1, Sinan Kazan2, Serdar Ceylaner3, Alper Emre Kurt4, Sena Ulu5 and Muhsin Elmas1
1Medical Genetics Department, Afyonkarahisar Health Sciences University, Faculty of Medicine, Afyonkarahisar, Turkey
2Internal Medicine and Nephrology Department, Afyonkarahisar Health Sciences University, Faculty of Medicine, Afyonkarahisar, Turkey
3Medical Genetics Department, Lokman Hekim University, Faculty of Medicine, Ankara, Turkey
4Internal Medicine Department, Afyonkarahisar Public Hospital, Afyonkarahisar, Turkey
5Internal Medicine and Nephrology Department, Bahcesehir University, Faculty of Medicine, Istanbul, Turkey
*Corresponding Author: Mujgan Ozdemir Erdogan, Medical Genetics Department, Afyonkarahisar Health Sciences University, Faculty of Medicine, Afyonkarahisar, Turkey.
October 21, 2022; Published: January 05, 2023
Objectıve: Mutational screening of the PKD1 and PKD2 genes, which are known to be associated with the severity of the disease, and the GANAB gene, which is a strong candidate gene, which is thought to be involved in the genetic basis of ADPKD, were performed in 16 cases admitted with the indication of autosomal dominant polycystic kidney disease (ADPKD).
Materıals and Methods: A total of 16 cases who were diagnosed with ADPKD and met the criteria were evaluated. After DNA isolation from peripheral blood samples of the case group, PCR was performed with primers designed specifically for PKD1, PKD2 and GANAB genes. In this study, targeted resequencing method was applied by using MiSeq (Illumina, San Diego, CA) system for mutation screening of the aforementioned genes. In the analysis of detected variants, in silico analyzes, database searches and literature reviews were performed. For this, Varsome, Polyphen2, HGMD-Public, PubMed, Google search, Clinvar, EXAC and 1,000 Genomes studies were used.
Results: As a result of the sequence analysis of PKD1, PKD2 and GANAB genes from 16 cases diagnosed with ADPKD, at least one of the 3 genes analyzed for all patients and at least one disease-related variant was detected. The changes found are all heterozygous changes.
Six PKD1 polymorphism were found in 4 patients. In 11 of 16 patients, 14 different variants for the PKD1 gene (2 frameshifts, 5 missense, 3 nonsense, 1spilice region and 3 synonyms) were detected. In 6 of 16 patients, 6 different variants (3 nonsense, 1 missense, 2 synonyms) were detected for the PKD2 gene with a pathogenic effect. As a result of the GANAB gene sequence analysis, 6 different variants (1 missense, 3 synonyms and 2 noncoding) were determined for 5 patients. Of the 27 non-polymorphic variants detected for these 3 genes, 5 are novel mutations that have not been reported before. Of these 5 mutations, 3 were found in the PKD1 gene, and 1 in each of the PKD2 and GANAB genes. While 6 of these mutations in 16 patients are de novo (fresh mutation), 10 of them have autosomal dominant inheritance.
Conclusıon: Our study results shed light on the genotype-phenotype correlation, the effect of genotype on clinical progression, and mutations not previously reported in the literature. In addition, our study results support that the GANAB gene is a strong candidate gene that plays a role in the genetic basis of ADPKD. It is recommended that similar studies be conducted with patient groups with a higher number of patients.
Keywords: Autosomal Dominant Polycystic Kidney Disease; PKD1 Gene; PKD2 Gene; GANAB Gene
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