Abstract: SA-PO412
Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis: Expression Pattern of Urinary Exosomal MiRNAs
Session Information
- Genetic Diseases of the Kidney - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1002 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Vall, Monica, Vall d'Hebron Institut de Recerca, Barcelona, Barcelona, Spain
- Duran, Monica, Vall d'Hebron Institut de Recerca, Barcelona, Barcelona, Spain
- Ariceta, Gema, Hospital Universitari Vall d' Hebron, Barcelona, Spain
- Meseguer, Anna, Vall d'Hebron Institut de Recerca, Barcelona, Spain
Group or Team Name
- Renal Physiopathology Group. VHIR
Background
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubulopathy caused by CLDN16 or CLDN19 genes mutations. FHHNC is characterized by urinary wasting of calcium and magnesium, nephrocalcinosis and progression to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Also, some CLDN19 patients develop ocular impairment. Patients homozygous for c.59G>A; p.G20D mutation in CLDN19 gene, the most frequent in Spain, exhibit different progression to kidney failure, suggesting that other molecular events modulate disease evolution. In absence of biopsy availability, urinary exosome-like vesicles (uEVs) are a non-invasive source of information of the renal condition. In this work we analyzed the expression pattern of miRNAs obtained from uEVs of FHHNC patients.
Methods
uEVs isolation of non-transplanted FHHNC patients was performed by differential centrifugation and miRNA cargo was extracted with miRCURY RNA Isolation kit and analyzed through microarray assays. Statistical parameters were p-value<0,5 and an absolute logFC>1, except for renal progression comparison which was 0,5.
Results
Our cohort comprises 30 patients: 3 present mutations in CLDN16 gene while 27 (90%) in CLDN19, of which, 63% (n=19) are p.G20D homozygous. Most patients (53%) exhibit a moderate renal phenotype whereas 17% and 30% are classified as severe and mild, respectively. In the ESRD group, 80% of patients were female, whilst in the non-ESRD group they represent only 40%. Comparisons revealed sets of deregulated miRNAs in FHHNC patients and specific miRNAs associated with the homozygous p.G20D mutation. Moreover, we identified two miRNAs differentially expressed in male patients and one related to renal disease progression.
Conclusion
The analysis of miRNAs defined a set of miRNAs commonly expressed in all FHHNC patients and other miRNAs exclusively associated with the homozygous p.G20D mutation in the CLDN19 gene. Furthermore, gender of patients and renal disease progression were also associated with specific miRNAs each.
Funding
- Government Support - Non-U.S.