ESPN 51th Annual Meeting

ESPN 2018

Susanna Negrisolo 2 Andrea Carraro 1 Giulia Fregonese 1 Davide Meneghesso 1 Germana Longo 1 Marco Castagnetti 2 Piergiorgio Gamba 3 Giorgio Valle 4 Luisa Murer 1

1- University-Hospital of Padova, Pediatric Nephrology, Dialysis and Transplant Unit, Department of Women’s and Children’s Health, Padua, Italy
2- University Hospital of Padova, Urology Unit, Department of Oncological and Surgical Sciences, Padua, Italy
3- University of Padova, Pediatric Surgery, Women’s and Children’s Health Department, Padua, Italy
4- University of Padova, CRIBI Biotechnology Centre, Padua, Italy

INVS gene encodes the ciliary structural protein Inversin, already known in kidney development pathway. INVS mutations are associated with infantile nephronophthisis (NPHP2), an autosomal recessive cystic kidney disease that leads to early end stage renal failure. In our previously Whole exome sequencing analysis in pediatric patient with renal hypo/dysplasia (RHD), we highlighted apatient with va compound heterozygous INVS mutation. This patient, without any NPHS2 features, had inherited these pathological variant by his healthy parents. This new study aim was to check the involvment of INVS mutations in the RHD determination by a INVS mutational screening in a larger RHD population.

Material and methods:

INVS coding  and flaking regions sequence were screened by High Resolution Melt Analysis and Sanger sequencing in 46 children with sporadic, non syndromic RHD, with or without upper urinary tract malformations. All patients enrolled did not have the NPHS2 common features.


To date, INVS mutational screened revealed 3 rare heterozygous variants in three patients: 2 missense (allele freq<0.0005) and one splice -site variant (allele freq<0.001). No causative recessive mutations has so far been identified in 40/46 patients.


The identified variants had very low frequency in public databases, therefore we could speculate that their distribuition could not be casual. Although a second intronic variation could not be evaluated in our screening, our findings do not exclude that INVS mutation could be associated to RHD phenotype. Future key step will be analysing INVS  non -coding regulatory regions considering also an increased number of patients.