Mutational screening of PKD1 and PKD2 in Indian ADPKD patients identified 95 genetic variants

Raj, Sonam; Singh, Rana Gopal; Das, Parimal

doi:10.1016/j.mrfmmm.2020.111718

Cited by 8 publications

(9 citation statements)

References 40 publications

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“…Analysis of the WES data identified several genetic variants within the PKD1 and PKD2 which are known to be major candidate genes of ADPKD. The variants in PKD1 were more prevalent in our cohort, consistent with previous reports highlighting the predominant role of PKD1 variants in ADPKD pathogenesis [17,24]. Variants identified in PKD1 included missense changes, nonsense variant, frameshift variants, and intronic splice site variants, each with varying degrees of pathogenicity as classified in ClinVar.…”

Section: Discussionsupporting

confidence: 90%

“…The all variants but one indentified in our cohort were different from those previously reported in our laboratory's work [17]. The absence of identified variants in population databases and their submission in ClinVar without corresponding population frequency data highlight the need for population-specific genetic studies to fully capture the spectrum of disease-causing variants, particularly in understudied populations such as the Indian cohort in our study.…”

Section: Discussioncontrasting

confidence: 73%

“…The PKD2 variants were also detected, albeit less frequently, emphasizing the contribution of both genes to ADPKD. [17,24,27,28]. The variants identified in the PKD1 affect various protein regions, each with its potential impact on the function of PC1 (Table 7).…”

Section: Discussionmentioning

confidence: 99%

“…The genomic DNA was isolated from peripheral blood samples using the standardized salting out method (14). DNA quality and quantity were estimated using both spectrophotometric (Nanodrop 2000, Thermo Scientific Inc.) and fluorometry-based (DNA Assay BR, Invitrogen, Cat# Q32853 / Qubit High Sensitivity Assay, Invitrogen,) methods.…”

Section: Sample Collection and Dna Extractionmentioning

confidence: 99%

“…The study received approval from the Institute Ethical Committee of the Institute of Science, Banaras Hindu University. Genomic DNA was extracted from peripheral blood samples using the standardized salting-out method [17]. Assessment of DNA quality and quantity was performed using spectrophotometric analysis (Nanodrop 2000, Thermo Scientific Inc.) or fluorometry-based methods (DNA Assay BR, Invitrogen, Cat# Q32853 / Qubit High Sensitivity Assay, Invitrogen).…”

Section: Sample Collection and Dna Isolationmentioning

confidence: 99%

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A Whole Exome Sequencing Study of a small Indian Autosomal Dominant Polycystic Kidney Disease Patient Cohort

Devi

Singh

Mohapatra

et al. 2023

Preprint

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Polycystic Kidney Disease (PKD), which affects 1 in 500 to 1000 people globally, is a monogenic, hereditary nephropathy marked by the gradual growth and expansion of many fluid-filled kidney cysts often resulting in end-stage renal disease. Even within the same family, ADPKD shows variation in phenotype, genotype, and disease severity. While PKD1 and PKD2 mutations account for the majority of ADPKD cases (75% and 15%, respectively), about 7% of cases are currently genetically unexplained. The ADPKD-associated genes GANAB, DNAJB11, and ALG9 are also found in several genetically unresolved cases. Being a large gene constituted with 46 exons covering a 52 kb area and a 14 kb transcript and with six pseudogenes, PKD1 poses a challenge for direct PCR and Sanger sequencing of all exons and exon intron boundaries for mutation analysis. In order to find the disease-causing mutation(s) in a trio, whole exome sequencing (WES) was carried out. In the affected mother and daughter, no pathogenic variation(s) in the PKD1, PKD2, DNAJB11, GANAB, and ALG9 candidate genes was observed. However, WES analysis identified a frameshift deletion [c.32del/p.Leu11ArgfsTer61] in MIOX as the most likely cause of the disease shared by both affected individuals. This has not previously been reported in ADPKD. Further, the differential gene expression profile analysis of the data of cysts from GEO database showed reduced expression of MIOX in cystic samples of ADPKD individuals as compared to minimal cystic tissues (MCT) and control tissue samples. Myo-Inositol Oxygenase, or MIOX, is an enzyme that specifically expresses in renal tubules and catalyses the initial step of the kidney-based myoinositol catabolism pathway. Both affected candidates also shared benign variants and other variations of uncertain significance which might function as modifiers in the development of the disease. Further functional analysis of the variation(s) will clarify whether and how MIOX contributes to the development of the disease.

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Section: Discussionsupporting

confidence: 90%

Section: Discussioncontrasting

confidence: 73%