Genetic heterogeneity of polycystic kidney disease in Bulgaria

Bogdanova, Nadja; Dworniczak, Bernd; Dragova, D.; Todorov, Vassil; Dimitrakov, D; Kalinov, Krassimir; Hallmayer, Joachim; Horst, Jürgen; Kalaydjieva, Luba

doi:10.1007/bf00209481

Cited by 62 publications

(34 citation statements)

References 31 publications

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“…This direct interaction is consistent with the clinical observation that patients with mutations of either PKD1 or PKD2 develop an identical phenotype of renal and extrarenal disease (although a milder form of the disease results from mutations of PKD2) (20,21). Evidence for the involvement of a third genetic locus in PKD includes the existence of diseases that resemble PKD and for which genetic linkage to PKD1 or PKD2 has been excluded (22)(23)(24)(25).…”

Section: Discussionsupporting

confidence: 85%

Genomic Organization and Functional Analysis of Murine PKD2L1

Murakami

Ohba

et al. 2005

Journal of Biological Chemistry

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Mutations in genes that encode polycystins 1 or 2 cause polycystic kidney disease (PKD). Here, we report the genomic organization and functional expression of murine orthologue of human polycystin-2L1 (PKD2L1). The murine PKD2L1 gene comprises 15 exons in chromosome 19C3. Coexpression of PKD2L1 together with polycystin-1 (PKD1) resulted in the expression of PKD2L1 channels on the cell surface, whereas PKD2L1 expressed alone was retained within the endoplasmic reticulum (ER). This suggested that interaction between PKD1 and PKD2L1 is essential for PKD2L1 trafficking and channel formation. Deletion analysis at the cytoplasmic tail of PKD2L1 revealed that the coiled-coil domain was important for trafficking by PKD1. Mutagenesis within two newly identified ER retention signal-like amino acid sequences caused PKD2L1 to be expressed at the cell surface. This indicated that the coiled-coil domain was responsible for retaining PKD2L1 within the ER. Functional analysis of murine PKD2L1 expressed in HEK 293 cells was undertaken using calcium imaging. Coexpression of PKD1 and PKD2L1 resulted in the formation of functional cation channels that were opened by hypo-osmotic stimulation, whereas neither molecule formed functional channels when expressed alone. We conclude that PKD2L1 forms functional cation channels on the plasma membrane by interacting with PKD1. These findings raise the possibility that PKD2L1 represents the third genetic locus that is responsible for PKD.

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Section: Discussionsupporting

confidence: 85%

Genomic Organization and Functional Analysis of Murine PKD2L1

Murakami

Ohba

et al. 2005

Journal of Biological Chemistry

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“…Another study was performed by colleagues on 48 Korean families that the results were composed of PKD1 (79%) and PKD2 (21%) (15). Moreover, the similar rate of the genetic heterogeneity has been shown in other populations, such as Argentinians (91%) (16), Bulgarians (73%) (17), and Caucasians (81%) (18). Radpour et al study, the closest one to our investigation, evaluated 15 Iranian families and reported that the proportion of families linked to PKD1, PKD2, or to other genes was 73%, 13%, and 13%, respectively (5).…”

Section: Discussionmentioning

confidence: 65%

Linkage Analysis of Autosomal Dominant Polycystic Kidney Disease in Iranian Families through PKD1 and PKD2 DNA Microsatellite Markers

et al. 2017

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Background: Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous disorder. Two known loci, including PKD1 (16p13.3) and PKD2 (4q21), as well as a third locus that is not clearly identified, cause ADPKD. Objectives: The aim of this study was to assess the genetic linkage of 4 linked microsatellite markers of PKD genes (PKD1 and PKD2) to ADPKD for genetic screening of familiar PKD patients in Yazd. Methods: This familial case-control study was conducted among 18 families. The linkage analysis was performed using 2 pairs of polymorphic microsatellite markers that are closely linked to the PKD1 gene (16AC2.5 and KG8) and 2 other pairs closely linked to the PKD2 gene (D4S231 and D4S423). These markers were detected through PCR of tandem repeats method and polyacrylamide gel electrophoresis. Results: The disease was linked to PKD1 about 77.8%, PKD2 16.7% of the families, and to neither gene in 5.5%, according to LOD scores and allele segregation analysis. It also found relatively high heterozygosity and polymorphism information contents (PIC) values for 3 markers including 16AC2.5 (PIC: 0.798) for PKD1 gene and D4S423 (PIC: 0.807) as well as D4S231 (PIC: 0.741) for PKD2 gene. However, it seems that KG8 marker has no significant linkage to the PKD1 gene (PIC: 0.329) among Yazd PKD patients. Conclusions: These results show similarity to another report from Iranian families and according to these similar results, it seems that 16AC2.5 and D4S423 markers would provide an improved framework for genetic screening of ADPKD patients among familiar PKD patients in Yazd.

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“…47 Some families with ADPKD display neither PKD1 nor PKD2 mutations, suggesting that other genetic loci may also be associated with the disease. [48][49][50][51][52] In general, these patients have milder disease, although a number of families with more severe clinical courses have been described. 52,53 Reasons for this phenotype heterogenicity are unclear, and it is possible that more than one unknown gene is causative in these unlinked families.…”

Section: Clinical Criteriamentioning

confidence: 99%

Polycystic kidney disease: inheritance, pathophysiology, prognosis, and treatment

Halvorson

Bremmer²,

Jacobs³

2010

IJNRD

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Both autosomal dominant and recessive polycystic kidney disease are conditions with severe associated morbidity and mortality. Recent advances in the understanding of the genetic and molecular pathogenesis of both ADPKD and ARPKD have resulted in new, targeted therapies designed to disrupt cell signaling pathways responsible for the abnormal cell proliferation, dedifferentiation, apoptosis, and fluid secretion characteristic of the disease. Herein we review the current understanding of the pathophysiology of these conditions, as well as the current treatments derived from our understanding of the mechanisms of these diseases.

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Genetic heterogeneity of polycystic kidney disease in Bulgaria

Cited by 62 publications

References 31 publications

Genomic Organization and Functional Analysis of Murine PKD2L1

Genomic Organization and Functional Analysis of Murine PKD2L1

Linkage Analysis of Autosomal Dominant Polycystic Kidney Disease in Iranian Families through PKD1 and PKD2 DNA Microsatellite Markers

Polycystic kidney disease: inheritance, pathophysiology, prognosis, and treatment

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