Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
June-2017 Volume 15 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2017 Volume 15 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Copy-number variation analysis in familial nonsyndromic congenital anomalies of the kidney and urinary tract: Evidence for the causative role of a transposable element-associated genomic rearrangement

  • Authors:
    • Ekaterini Siomou
    • Artemis G. Mitsioni
    • Vasileios Giapros
    • Ioanna Bouba
    • Dimitrios Noutsopoulos
    • Ioannis Georgiou
  • View Affiliations / Copyright

    Affiliations: Department of Pediatrics, University Hospital of Ioannina, Ioannina 45500, Greece, Laboratory of Medical Genetics and Human Reproduction, Faculty of Medicine, University of Ioannina, Ioannina 45500, Greece, Neonatal Intensive Care Unit, University Hospital of Ioannina, Ioannina 45500, Greece, Laboratory of General Biology, Faculty of Medicine, University of Ioannina, Ioannina 45500, Greece
    Copyright: © Siomou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3631-3636
    |
    Published online on: April 12, 2017
       https://doi.org/10.3892/mmr.2017.6462
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Most congenital anomalies of the kidney and urinary tract (CAKUT) are sporadic, but familial occurrence has been described, suggesting a genetic contribution. Copy‑number variations (CNVs) were detected in patients with CAKUT to identify possible novel genomic regions associated with CAKUT. CNVs were investigated in 7 children with CAKUT from three unrelated families using array comparative genomic hybridization: female monozygotic twins with bilateral duplex collecting system/vesicoureteral reflux (VUR)/unilateral renal hypodyspasia (URHD); two male siblings with VUR/URHD; 3 male second cousins, one with bilateral VUR/URHD, one with bilateral VUR and one with ureterovesical junction obstruction (UVJO). Five patients had a normal constitution of CNVs, one had a duplication of 0.2 Mb on the 5q‑arm (5q23.3), probably unrelated to CAKUT, and one with UVJO had a 1.4 Mb deletion on the 17q‑arm (17q12) which includes a known CAKUT gene, HNF1B. The phenotype of HNF1B deletion was extended including renal magnesium wasting. A higher coverage in transposable elements (TEs) was found in the deleted region compared with the expected density in any random genomic region. Notably, the 5' breakpoint was mapped within a solo long terminal repeat (LTR) sequence. Moreover, highly similar members of solo LTR and mammalian interspersed repetitive (MIR) elements, as well as nucleotide sequence microhomology were detected at the breakpoint regions. In conclusion, the deletion detected in one patient suggests this genomic imbalance as causative for UVJO. A not very well known phenotype of HNF1B deletion resulting in both low urinary tract malformations and renal wasting of magnesium was described. The high load in TEs of the deleted region, the presence of highly similar elements, and the microhomology found at breakpoint regions may have contributed to the generation of the deletion. CNV analysis could reveal novel causative genomic regions in patients with CAKUT, and further studies in larger cohorts are needed.
View Figures

Figure 1

Figure 2

View References

1 

Melo BF, Aguiar MB, Bouzada MC, Aguiar RL, Pereira AK, Paixão GM, Linhares MC, Valerio FC, Simões E Silva AC and Oliveira EA: Early risk factors for neonatal mortality in CAKUT: Analysis of 524 affected newborns. Pediatr Nephrol. 27:965–972. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Weber S, Landwehr C, Renkert M, Hoischen A, Wühl E, Denecke J, Radlwimmer B, Haffner D, Schaefer F and Weber RG: Mapping candidate regions and genes for congenital anomalies of the kidneys and urinary tract (CAKUT) by array-based comparative genomic hybridization. Nephrol Dial Transplant. 26:136–143. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Hwang DY, Dworschak GC, Kohl S, Saisawat P, Vivante A, Hilger AC, Reutter HM, Soliman NA, Bogdanovic R, Kehinde EO, et al: Mutations in 12 known dominant disease-causing genes clarify many congenital anomalies of the kidney and urinary tract. Kidney Int. 85:1429–1433. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Caruana G, Wong MN, Walker A, Heloury Y, Webb N, Johnstone L, James PA, Burgess T and Bertram JF: Copy-number variation associated with congenital anomalies of the kidney and urinary tract. Pediatr Nephrol. 30:487–495. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Hancks DC and Kazazian HH Jr: Active human retrotransposons: Variation and disease. Curr Opin Genet Dev. 22:191–203. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Kidd JM, Graves T, Newman TL, Fulton R, Hayden HS, Malig M, Kallicki J, Kaul R, Wilson RK and Eichler EE: A human genome structural variation sequencing resource reveals insights into mutational mechanisms. Cell. 143:837–847. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Hancks DC and Kazazian HH Jr: Roles for retrotransposon insertions in human disease. Mob DNA. 7:92016. View Article : Google Scholar : PubMed/NCBI

8 

Elisaf M, Panteli K, Theodorou J and Siamopoulos KC: Fractional excretion of magnesium in normal subjects and in patients with hypomagnesemia. Magnes Res. 10:315–320. 1997.PubMed/NCBI

9 

Bianchetti MG, Edefonti A and Bettinelli A: The biochemical diagnosis of Gitelman disease and the definition of ‘hypocalciuria’. Pediatr Nephrol. 18:409–411. 2003.PubMed/NCBI

10 

Medical versus surgical treatment of primary vesicoureteral reflux: Report of the International Reflux Study Committee. Pediatrics. 67:392–400. 1981.PubMed/NCBI

11 

Sanna-Cherchi S, Kiryluk K, Burgess KE, Bodria M, Sampson MG, Hadley D, Nees SN, Verbitsky M, Perry BJ, Sterken R, et al: Copy-number disorders are a common cause of congenital kidney malformations. Am J Hum Genet. 91:987–997. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Westland R, Verbitsky M, Vukojevic K, Perry BJ, Fasel DA, Zwijnenburg PJ, Bökenkamp A, Gille JJ, Saraga-Babic M, Ghiggeri GM, et al: Copy number variation analysis identifies novel CAKUT candidate genes in children with a solitary functioning kidney. Kidney Int. 88:1402–1410. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Lindner TH, Njolstad PR, Horikawa Y, Bostad L, Bell GI and Sovik O: A novel syndrome of diabetes mellitus, renal dysfunction and genital malformation associated with a partial deletion of the pseudo-POU domain of hepatocyte nuclear factor-1beta. Hum Mol Genet. 8:2001–2008. 1999. View Article : Google Scholar : PubMed/NCBI

14 

Nakayama M, Nozu K, Goto Y, Kamei K, Ito S, Sato H, Emi M, Nakanishi K, Tsuchiya S and Iijima K: HNF1B alterations associated with congenital anomalies of the kidney and urinary tract. Pediatr Nephrol. 25:1073–1079. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Thomas R, Sanna-Cherchi S, Warady BA, Furth SL, Kaskel FJ and Gharavi AG: HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort. Pediatr Nephrol. 26:897–903. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Coffinier C, Barra J, Babinet C and Yaniv M: Expression of the vHNF1/HNF1beta homeoprotein gene during mouse organogenesis. Mech Dev. 89:211–213. 1999. View Article : Google Scholar : PubMed/NCBI

17 

Kolatsi-Joannou M, Bingham C, Ellard S, Bulman MP, Allen LI, Hattersley AT and Woolf AS: Hepatocyte nuclear factor-1beta: A new kindred with renal cysts and diabetes and gene expression in normal human development. J Am Soc Nephrol. 12:2175–2180. 2001.PubMed/NCBI

18 

Adalat S, Woolf AS, Johnstone KA, Wirsing A, Harries LW, Long DA, Hennekam RC, Ledermann SE, Rees L, van't Hoff W, et al: HNF1B mutations associate with hypomagnesemia and renal magnesium wasting. J Am Soc Nephrol. 20:1123–1131. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Murray PJ, Thomas K, Mulgrew CJ, Ellard S, Edghill EL and Bingham C: Whole gene deletion of the hepatocyte nuclear factor-1beta gene in a patient with the prune-belly syndrome. Nephrol Dial Transplant. 23:2412–2415. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Meij IC, Koenderink JB, Van Bokhoven H, Assink KF, Groenestege WT, de Pont JJ, Bindels RJ, Monnens LA, van den Heuvel LP and Knoers NV: Dominant isolated renal magnesium loss is caused by misrouting of the Na(+),K(+)-ATPase gamma-subunit. Nat Genet. 26:265–266. 2000. View Article : Google Scholar : PubMed/NCBI

21 

Nicolaou N, Renkema KY, Bongers EM, Giles RH and Knoers NV: Genetic, environmental, and epigenetic factors involved in CAKUT. Nat Rev Nephrol. 11:720–731. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Schedl A: Renal abnormalities and their developmental origin. Nat Rev Genet. 8:791–802. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Friedli M and Trono D: The developmental control of transposable elements and the evolution of higher species. Annu Rev Cell Dev Biol. 31:429–451. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Babatz TD and Burns KH: Functional impact of the human mobilome. Curr Opin Genet Dev. 23:264–270. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Mandal PK and Kazazian HH Jr: SnapShot: Vertebrate transposons. Cell. 135:192.e12008. View Article : Google Scholar

26 

Pearson CE, Edamura K Nichol and Cleary JD: Repeat instability: Mechanisms of dynamic mutations. Nat Rev Genet. 6:729–742. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Koumbaris G, Hatzisevastou-Loukidou H, Alexandrou A, Ioannides M, Christodoulou C, Fitzgerald T, Rajan D, Clayton S, Kitsiou-Tzeli S, Vermeesch JR, et al: FoSTeS, MMBIR and NAHR at the human proximal Xp region and the mechanisms of human Xq isochromosome formation. Hum Mol Genet. 20:1925–1936. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Siomou E, Mitsioni AG, Giapros V, Bouba I, Noutsopoulos D and Georgiou I: Copy-number variation analysis in familial nonsyndromic congenital anomalies of the kidney and urinary tract: Evidence for the causative role of a transposable element-associated genomic rearrangement. Mol Med Rep 15: 3631-3636, 2017.
APA
Siomou, E., Mitsioni, A.G., Giapros, V., Bouba, I., Noutsopoulos, D., & Georgiou, I. (2017). Copy-number variation analysis in familial nonsyndromic congenital anomalies of the kidney and urinary tract: Evidence for the causative role of a transposable element-associated genomic rearrangement. Molecular Medicine Reports, 15, 3631-3636. https://doi.org/10.3892/mmr.2017.6462
MLA
Siomou, E., Mitsioni, A. G., Giapros, V., Bouba, I., Noutsopoulos, D., Georgiou, I."Copy-number variation analysis in familial nonsyndromic congenital anomalies of the kidney and urinary tract: Evidence for the causative role of a transposable element-associated genomic rearrangement". Molecular Medicine Reports 15.6 (2017): 3631-3636.
Chicago
Siomou, E., Mitsioni, A. G., Giapros, V., Bouba, I., Noutsopoulos, D., Georgiou, I."Copy-number variation analysis in familial nonsyndromic congenital anomalies of the kidney and urinary tract: Evidence for the causative role of a transposable element-associated genomic rearrangement". Molecular Medicine Reports 15, no. 6 (2017): 3631-3636. https://doi.org/10.3892/mmr.2017.6462
Copy and paste a formatted citation
x
Spandidos Publications style
Siomou E, Mitsioni AG, Giapros V, Bouba I, Noutsopoulos D and Georgiou I: Copy-number variation analysis in familial nonsyndromic congenital anomalies of the kidney and urinary tract: Evidence for the causative role of a transposable element-associated genomic rearrangement. Mol Med Rep 15: 3631-3636, 2017.
APA
Siomou, E., Mitsioni, A.G., Giapros, V., Bouba, I., Noutsopoulos, D., & Georgiou, I. (2017). Copy-number variation analysis in familial nonsyndromic congenital anomalies of the kidney and urinary tract: Evidence for the causative role of a transposable element-associated genomic rearrangement. Molecular Medicine Reports, 15, 3631-3636. https://doi.org/10.3892/mmr.2017.6462
MLA
Siomou, E., Mitsioni, A. G., Giapros, V., Bouba, I., Noutsopoulos, D., Georgiou, I."Copy-number variation analysis in familial nonsyndromic congenital anomalies of the kidney and urinary tract: Evidence for the causative role of a transposable element-associated genomic rearrangement". Molecular Medicine Reports 15.6 (2017): 3631-3636.
Chicago
Siomou, E., Mitsioni, A. G., Giapros, V., Bouba, I., Noutsopoulos, D., Georgiou, I."Copy-number variation analysis in familial nonsyndromic congenital anomalies of the kidney and urinary tract: Evidence for the causative role of a transposable element-associated genomic rearrangement". Molecular Medicine Reports 15, no. 6 (2017): 3631-3636. https://doi.org/10.3892/mmr.2017.6462
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team