ESPN 54th Annual Meeting

ESPN 2022


 
PATIENTS WITH CONGENITAL ANOMALIES OF KIDNEY AND URINARY TRACT (CAKUT) SHARE COMMON HOTSPOT LOCI WITH LOW FREQUENCY VARIANTS
JAKOB ZAPUšEK 1 MARIO GORENJAK 2 DANIJELA KRGOVIć 3 NATAšA MARčUN VARDA 4

1- DEPARTMENT OF PAEDIATRICS, GENERAL HOSPITAL PTUJ, POTRčEVA CESTA 23, 2250 PTUJ
2- UNIVERSITY OF MARIBOR, FACULTY OF MEDICINE, CENTRE FOR HUMAN MOLECULAR GENETICS AND PHARMACOGENOMICS, TABORSKA ULICA 8, 2000 MARIBOR, SLOVENIA
3- LABORATORY OF MEDICAL GENETICS, UNIVERSITY MEDICAL CENTRE MARIBOR, LJUBLJANSKA 5, 2000, MARIBOR, SLOVENIA
4- DEPARTMENT OF PAEDIATRICS, NEPHROLOGY UNIT, UNIVERSITY MEDICAL CENTRE MARIBOR, LJUBLJANSKA 5, 2000, MARIBOR, SLOVENIA
 
Introduction:

 

Congenital anomalies of kidney and urinary tract (CAKUT) are common

pathology and important cause of chronic kidney disease in children. The aim of our study

was to find genetic correlations between our cohort of children with severe CAKUT

phenotypes and relevant genetic findings, using next-generation sequencing (NGS).

Material and methods:

 

Cinical study was performed including 324

CAKUT patients, who

had a blood sample for DNA isolation withdrawn. Afterwards, 113 patients with most severe CAKUT were selected for Whole Exome Next-

generation sequencing using NovaSeq 6000 Sequencing System and Agilents' SureSelect

Human All Exon V6 workflow. All enrolled children had more than one CAKUT and almost

all of them ( 93.8%) had vesicoureteral reflux (VUR).

Results:

 

We found 11 very low population frequency variants (mutations/insertions/deletions)

that were present in all 113 patients. 7 of them were splice region mutations, 3 frameshift

mutations and 1 missense mutation. Every locus with identified variants in all 113 patients

presents many insertions/deletions, thus each locus can be interpreted as a mutation hotspot.

Two MUC16 variants on chromosome 19 have been also discovered and may contribute to the

phenotype as compound heterozygous mutations if present in different alleles. Further

research in terms of genetic testing of parents is needed to elucidate the role of MUC16 in

CAKUT. We hypothesise that compound heterozygous variants in MUC16 may present a

 

monogenic VUR aetiology.

Conclusions:

 

In every single included patient with severe CAKUT 11 mutual mutations were

found, which is rather uncommon in such studies, promising important findings, warranting

further elucidation and confirmation. Both mutations on chromosome 19 are especially

interesting as they may present a monogenic VUR aetiology in terms of compound

heterozygote.