ESPN 51th Annual Meeting

ESPN 2018


 
Frequency of Pathogenic Variants in a Munich CAKUT cohort
KORBINIAN M. RIEDHAMMER 1 MICHAELA STIPPEL 1 ROMAN GÜNTHNER 2 MATTHIAS C. BRAUNISCH 2 PIERRE MAURICE HERR 1 EVA PAULINE MACHEROUX 1 BODO B. BECK 3 ROBIN SATANOVSKIJ 2 VELIBOR TASIC 4 JULIA HOEFELE 1

1- INSTITUTE OF HUMAN GENETICS, KLINIKUM RECHTS DER ISAR, TECHNICAL UNIVERSITY OF MUNICH, MUNICH, GERMANY
2- DEPARTMENT OF NEPHROLOGY, KLINIKUM RECHTS DER ISAR, TECHNICAL UNIVERSITY OF MUNICH, MUNICH, GERMANY
3- INSTITUTE OF HUMAN GENETICS, UNIVERSITY OF COLOGNE, COLOGNE, GERMANY
4- MEDICAL FACULTY SKOPJE, UNIVERSITY CHILDREN’S HOSPITAL, SKOPJE, MACEDONIA
 
Introduction:

Congenital anomalies of the kidney and urinary tract (CAKUT) represent the major cause of chronic kidney disease before 25 years of age. It is highly clinically and genetically heterogeneous and therefore next-generation sequencing (NGS) has become a useful tool for the unbiased detection of pathogenic variants. The aim of this study was to evaluate the frequency of pathogenic variants in a Munich CAKUT cohort. Furthermore, we will present overall data of more than 200 families with a presumed hereditary kidney disorder.

Material and methods:

The clinical phenotype of the patients was collected using a standardized questionnaire. Mutational analysis was performed by exome sequencing (ES) or other molecular diagnostic techniques if needed.

Results:

The overall diagnostic yield with a presumed hereditary kidney disease was 54%. Concerning CAKUT, the study population consisted of 30 different families with a total of 68 individuals. 31 of them were healthy, 37 suffered from CAKUT. In 8 out of 30 families causative variants in known CAKUT genes have been identified. Therefore, the overall diagnostic yield in our CAKUT cohort was 27%. Three families had a variant in HNF1B (37.5%), two in PBX1 (25%), and one family each in SIX2 (12.5%), PAX2 (12.5%) or EYA1 (12.5%). Moreover, in a consanguineous family with two affected children a homozygous most likely pathogenic variant in a new candidate gene has been identified.

Conclusions:

In our cohort of both sporadic and familial CAKUT cases as well as in the complete cohort, we could reach a better diagnostic yield compared to the literature. ES has proven to be a valuable means of diagnostics in CAKUT and hereditary kidney diseases. Nevertheless, our above average diagnostic yield also stems from the fact of well-selected patients. Therefore, precise phenotyping is essential for the successful genetic work-up of nephrogenetic cases.