AUTHOR=Stippel Michaela , Riedhammer Korbinian M. , Lange-Sperandio Bärbel , Geßner Michaela , Braunisch Matthias C. , Günthner Roman , Bald Martin , Schmidts Miriam , Strotmann Peter , Tasic Velibor , Schmaderer Christoph , Renders Lutz , Heemann Uwe , Hoefele Julia 

TITLE=Renal and Skeletal Anomalies in a Cohort of Individuals With Clinically Presumed Hereditary Nephropathy Analyzed by Molecular Genetic Testing

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.642849

DOI=10.3389/fgene.2021.642849

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Chronic kidney disease (CKD) in childhood and adolescence occurs with a median incidence of 9 per million of the age-related population. Over 70% of CKD cases under the age of 25 years can be attributed to a hereditary kidney disease. Among these are hereditary podocytopathies, ciliopathies and (monogenic) congenital anomalies of the kidney and urinary tract (CAKUT). These disease entities can present with a vast variety of extrarenal manifestations. So far, skeletal anomalies (SA) have been infrequently described as extrarenal manifestation in these entities. The aim of this study was to retrospectively investigate a cohort of individuals with hereditary podocytopathies, ciliopathies or CAKUT, in which molecular genetic testing had been performed, for the extrarenal manifestation of SA.</p><p><bold>Material and Methods:</bold> A cohort of 65 unrelated individuals with a clinically presumed hereditary podocytopathy (focal segmental glomerulosclerosis, steroid resistant nephrotic syndrome), ciliopathy (nephronophthisis, Bardet-Biedl syndrome, autosomal recessive/dominant polycystic kidney disease), or CAKUT was screened for SA. Data was acquired using a standardized questionnaire and medical reports. 57/65 (88%) of the index cases were analyzed using exome sequencing (ES).</p><p><bold>Results:</bold> 8/65 (12%) index individuals presented with a hereditary podocytopathy, ciliopathy, or CAKUT and an additional skeletal phenotype. In 5/8 families (63%), pathogenic variants in known disease-associated genes (1x <italic>BBS1</italic>, 1x <italic>MAFB</italic>, 2x <italic>PBX1</italic>, 1x <italic>SIX2</italic>) could be identified.</p><p><bold>Conclusions:</bold> This study highlights the genetic heterogeneity and clinical variability of hereditary nephropathies in respect of skeletal anomalies as extrarenal manifestation.</p>