For the last 3 years, the MMC has taken part in collaborative studies for identification of genetic factors involved in several inherited renal conditions with clinicians from the Paediatric Nephrology Clinic, Department of Paediatrics. Our efforts are focused on steroid resistant nephritic syndrome (SRNS) and congenital anomalies of the kidney and urinary tract (CAKUT).
SRNS is a debilitating paediatric disease because of the limited therapeutic options. Our team, consisting of both geneticists from MMC and paediatric nephrologists from the Paediatric Nephrology Clinic, carried out a pilot study for determining the impact of the mutations in two genes, NPHS2 and WT1, in Bulgarian patients. The study was the first of its kind and will help to establish new diagnostic and counselling procedures for SRNS families. At the same time, the collection of genetically and phenotypically well characterised SRNS patients will be subject to additional studies for identification of novel genetic factors contributing to the disease.
CAKUT is a group of diverse pathologies, which together are the leading cause for chronic renal insufficiency and chronic renal failure in children. Very few genes have been shown to result in CAKUT in few patients, while at the same time individuals with similar mutations show variable phenotype – from complete absence of disease to very severe malformations. It is now clear that CAKUT is a group of multifactorial disorders, arising due to defect of different genes and characterised with complex interaction between genes and genes and environment. Initially, our efforts are focused on collection of affected families and complete phenotypic evaluation of the patients. This will be followed by mutations screening in few genes that have been shown to be associated with CAKUT, namely, TCF2, PAX2, EYE1 and SALLI. Finally, a genotype-phenotype correlation will be performed. As a result, we hope to collect a sizable cohort of patients with well documented phenotype and initial evaluation of genetic background. This will serve as basis for establishing novel collaborations on national and international level and will help for elucidation of the genetic and environmental factors involved in CAKUT. Ultimately, the research will lead to development of new protocols for genetic testing and counselling for the affected families, improved treatment and better prognosis for disease development.
Assoc. Prof. Anelia Boueva, MD, PhD, Paediatric Nephrology Clinic
Svetla Marinova, MD , PhD, Paediatric Nephrology Clinic
Georgi Roussinov, MD, Paediatric Nephrology Clinic
Galia Zlatanova-Rashkova, MD, Paediatric Nephrology Clinic
Polina Miteva, MD, Paediatric Nephrology Clinic