ESPN 51th Annual Meeting

ESPN 2018


 
Steroid Resistant Nephrotic Syndrome and Alport Syndrome Genetics: which relation?
Daniela Molino 1 Serena Ascione 1 Bruno Minale 1 Lorenza Lepore 1 Francesca Nuzzi 1 Elena Bresin 2 Carmine Pecoraro 1

1- Unit of Nephrology and Dialysis, Children Hospital Santobono, Naples, Italy
2- IRCCS-ISTITUTO DI RICERCHE FARMACOLOGICHE "MARIO NEGRI," CENTRO DI RICERCHE CLINICHE PER LE MALATTIE RARE "ALDO E CELE DACCò," RANICA BERGAMO, ITALY
 
Introduction:

Steroid Resistant Nephrotic Syndrome (SRNS) represents 15% of Nephrotic Syndromes in pediatric population and often recognizes genetic basis. Newer genomic technologies such as next-generation sequencing (NGS) are rapidly evolving and may improve with new insights into disease pathogenesis, diagnosis, genetics or prognosis.

Material and methods:

We selected 3 Steroid-CsA Resistant NS  patients differing in age of onset and family history; 2 of these were 1 year old and had negative history; the third was 15years and  had nephritis in his family history. No other symptoms were detectable. We performed  renal biopsy and NGS

Results:

Renal biopsy showed Minimal Change Disease (MCD) in all patients.

NGS showed variants in  COl4A3/4/5 genes associated with Alport syndrome, 1 also in MYH9 gene associated with Fetchner Syndrome:

Patient 1.Gene COL4A4 variant in heterozygosity g.227927312C>T, c.19990G>A, Gene COL4A3 variant in heterozygosity g.228029433C>T, c.-10C> T;

Patient 2.Gene COL4A3 variant in heterozygosity g.228144530C>G, c.2147C>G, Gene MYH9 variant in heterozygosity g.36681163G>C, c.5483+4C>G, Gene COQ22 variant in heterozygosity g.84205748C>G, c.320G>C;

Patient 3.Gene COL4A5 variant in hemizigosis c.1992G>T, p.K664N.

Patients were also screened for Alport and Fetchner Syndrome involved organs which showed no hematuria, hearing loss, ocular abnormalities or platelet number

Conclusions:

All the Steroid-CsA-Resistant NS  patients showed  variant  in COl4A3/4/5 genes associated with Alport syndrome and one  in MYH9 associated with Fetchner Syndrome. This finding is increasingly been described in some patients with FSGS and with MCD. It opens new scenarios to the mechanisms beneath Nephrotic Syndrome. We suggest to extend NGS to all SRNS patients to correlate genetic abnormalities to the ultrastructural changes of the glomerular basement membrane, that can lead to proteinuric nephropathies unresponsive to common therapies