NGS nominated CELA1, HSPG2, and KCNK5 as candidate genes for predisposition to balkan endemic nephropathy(Article)(Open Access)
- aDepartment of Medical Genetics, Medical University of Sofia, Zdrave Street 2, 1431 Sofia, Bulgaria
- bGenomics Laboratory of Malinov Clinic, 1620 Sofia, Bulgaria
- cVratza District Hospital, 66 Vtori Iuni Boulevard, 3000 Vratza, Bulgaria
- dFaculty of Medicine, University of Nis, Univerzitetski trg 2, 18000 Nis, Serbia
- eFaculty of Medicine, University of Skopje, Macedonian Academy of Sciences and Arts, Bul. Krste Misirkov 2, 1000 Skopje, North Macedonia
- fInstitute of Microbiology, Bulgarian Academy of Sciences, 26 Georgi Bonchev Street, 1113 Sofia, Bulgaria
- gNational Center of Public Health and Analyses, 15 Acad. Ivan Evst. Geshov Boulevard, 1431 Sofia, Bulgaria
- hInstitute of Anatomy, Bern University, Baltzerstrass 2, 3012 Bern, Switzerland
Abstract
Balkan endemic nephropathy (BEN) is a familial chronic tubulointerstitial disease with insidious onset and slow progression leading to terminal renal failure. The results of molecular biological investigations propose that BEN is a multifactorial disease with genetic predisposition to environmental risk agents. Exome sequencing of 22 000 genes with Illumina Nextera Exome Enrichment Kit was performed on 22 DNA samples (11 Bulgarian patients and 11 Serbian patients). Software analysis was performed via NextGene, Provean, and PolyPhen. The frequency of all annotated genetic variants with deleterious/damaging effect was compared with those of European populations. Then we focused on nonannotated variants (with no data available about them and not found in healthy Bulgarian controls). There is no statistically significant difference between annotated variants in BEN patients and European populations. From nonannotated variants with more than 40% frequency in both patients' groups, we nominated 3 genes with possible deleterious/damaging variants - CELA1, HSPG2, and KCNK5. Mutant genes (CELA1, HSPG2, and KCNK5) in BEN patients encode proteins involved in basement membrane/extracellular matrix and vascular tone, tightly connected to process of angiogenesis. We suggest that an abnormal process of angiogenesis plays a key role in the molecular pathogenesis of BEN. © 2014 D. Toncheva et al.
Indexed keywords
| EMTREE drug terms: | chymotrypsin like elastase family member 1DNAelastaseheparan sulfate proteoglycan 2potassium channelpotassium channel KCNK5proteoheparan sulfateunclassified drugCELA1 protein, humanKCNK5 protein, humanpancreatic elastaseperlecanproteoheparan sulfatetandem pore domain potassium channel |
|---|---|
| EMTREE medical terms: | articleBalkan endemic nephropathybasement membraneblood vessel toneclinical articlecontrolled studyexomeextracellular matrixgene deletiongene frequencygenetic predispositiongenetic variabilityhumaninterstitial nephritischronic kidney failuregeneticsgenotypehigh throughput sequencinginterstitial nephritispathology |
| MeSH: | Balkan NephropathyExomeGenetic Predisposition to DiseaseGenotypeHeparan Sulfate ProteoglycansHigh-Throughput Nucleotide SequencingHumansKidney Failure, ChronicPancreatic ElastasePotassium Channels, Tandem Pore Domain |
Chemicals and CAS Registry Numbers:
DNA, 9007-49-2; elastase, 9004-06-2; pancreatic elastase; perlecan, 143972-95-6;
CELA1 protein, human; Heparan Sulfate Proteoglycans; KCNK5 protein, human; Pancreatic Elastase; perlecan; Potassium Channels, Tandem Pore Domain
- ISSN: 23146133
- Source Type: Journal
- Original language: English
- DOI: 10.1155/2014/920723
- PubMed ID: 24949484
- Document Type: Article
- Publisher: Hindawi Publishing Corporation
Toncheva, D.; Department of Medical Genetics, Medical University of Sofia, Zdrave Street 2, Bulgaria;
© Copyright 2014 Elsevier B.V., All rights reserved.
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