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POSTERIOR URETHRAL VALVES: ONLY A TINY MEMBRANE?
Alice FAURE
1
, Georgina CARUANA
2
, Amanda WALKER
3
, Mili WONG
2
, Aurore BOUTY
1
, Mike O'BRIEN
1
, John Frederick
BERTRAM,
2
and Yves HELOURY
1
1) Royal Children's Hospital, Urology Department, Melbourne, AUSTRALIA - 2) Monash University, Department of
Anatomy and Developmental Biology, Melbourne, AUSTRALIA - 3) Royal Children's Hospital, Nephrology Department,
Melbourne, AUSTRALIA
PURPOSE
Despite the high incidence of congenital anomalies of the kidney and urinary tract (CAKUT), the genetic mutations
responsible for the majority of cases remain unknown. Some familial cases of posterior urethral valves (PUV) have been
described. The goal of this study was to assess the presence of sub-microscopic chromosomal inbalances
(microdeletions and microduplications) by molecular karyotyping in a cohort of PUV patients.
MATERIAL AND METHODS
224 patients with CAKUT were prospectively included between September 2012-March 2015. Forty-six (20.5%) had
PUV. With provided informed consent, genomic DNA was isolated from peripheral blood samples.
RESULTS
Copy number variations (CNV) were detected in 18 patients with CAKUT (8%). Of the 18 patients with CNV, patients
diagnosed with PUV were the most frequent (n=7, 39%), followed by VUR (n=4; 22%) and MCDK (n=3; 17%). CNV
were detected in 15.2% of PUV patients (7/46). Duplications were identified in 5 patients, deletions in 2. Parents from
5/7 cases harbouring CNVs participated in the study and revealed a de novo mutation in 1 case and 4 inherited
paternally cases. Among the seven patients with CNV, nearly 60 genes were contained in the altered genomic regions.
CONCLUSIONS
Our data reveals a significant contribution of a duplication-type CNV, mostly inherited, to PUV malformation. Novel
genomic regions were identified providing a list of PUV causing candidate genes. In a selected population of valve
patients, further studies will be conducted in order to correlate the genotype-phenotype and determine the potential
implication of CNV in the renal function prognosis.