April 2015 Vol. 3 No. 4

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Original Research Article

A pilot study conducted in the Czech Republic relating to the molecular analysis of the RET and GDNF genes in patients with cakut, predominantly unilateral renal agenesis

Zdenek Musil^1,2*, Iveta Svobodova¹*, Anasstasiya Zidkova¹, Marketa Safarikova¹ Ales Vicha², Michal Vocka³, Libor Stanek⁴, Tatiana Labudova², Josef Vcelak⁵, Eliska Vaclavikova⁵, Vladimír Tesar⁶, Petra Tesarova³, Tomas Seeman⁷ and Jana Reiterova⁶
 

¹Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic
²Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol in Prague, Czech Republic
³Department of Oncology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic
⁴Institute of Pathology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic
⁵Institute of Endocrinology, Prague, Czech Republic
⁶Department of Nephrology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic
⁷Department of Paediatrics of the 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol in Prague, Czech Republic

*Coressponding Author’s E-mail: musil.z@seznam.cz
Tel.: +420-224968164; Fax.: +420-224918666

Accepted March 30, 2015

Abstract

Renal anomalies are quite a common medical condition thought to be genetically influenced. The subject of this work was to conduct molecular genetic analysis of two human renal agenesis causing candidate genes encoding the RET receptor thyrosin kinase and GDNF neutrophic factor. The mutational analysis of twenty RET exons and three GDNF exons in twenty patients diagnosed with unilateral renal agenesis was carried out. Furthermore, copy number changes in both genes were investigated. The aim of this work was to identify potential mutations of RET/GDNF genes and thus to prove their association with renal agenesis. In this group of patients, no known pathogenic mutations were discovered, only three known single nucleotide polymorphisms of the RET gene were detected. Polymorphism rs1800860 (GCG-GCA, Ala432) was detected in 11/20 patients, two of them in a homozygous state. Polymorphism rs1800861 (CTT-CTG, Leu769) was identified in 6/20 patients, where one patient was a homozygote for the minor allele G. Polymorphism rs1800863 (TCC-TCG, Ser904) was detected in 5/20 patients, always in heterozygous combinations. All these polymorphisms are common ones with the minor allele frequency in population higher than 10%. Results of this study did not confirm an increased incidence of RET and GDNF mutations in patients diagnosed with renal agenesis and thus the association of these genes with renal agenesis cannot be proved. Nevertheless, with regard to a limited size of the patient group, the association between RET/GDNF signal complex and renal agenesis cannot be excluded. Submitted paper is a pilot study of patients with CAKUT in the Czech Republic, we intend to continue collecting samples and examine more genes relating to these anomalies.

Keywords: CAKUT, GDNF, Pheochromocytoma, Polymorphism, Renal agenesis, RET