Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disorder caused by mutations in CLDN16 or CLDN19 genes. This disease is characterized by massive urinary wasting of magnesium and calcium, nephrocalcinosis and inexorable progression to chronic kidney disease which leads to renal replacement therapy and kidney transplantation. Patients homozygous for p.G20D mutation in CLDN19 gene, the most frequent mutation in Spain and southern Europe, exhibit different progression to kidney failure. That suggests that beyond the pathogenic mutation itself, other molecular events are favoring disease progression. Since biopsy is not clinically indicated, urinary exosomes can be envisioned as a valuable non-invasive source of information of events occurring in kidney. In this work, we clinically classified the patients of our cohort with confirmed genetic diagnosis and analyzed the differential expression of their urinary exosomal miRNAs, by microarrays techniques. Comparisons among different groups revealed sets of deregulated miRNAs in FHHNC patients, as well as specific miRNAs associated with the homozygous p.G20D mutation, when compared with the control group. Moreover, we identified some miRNA differentially expressed in male and in female patients and others related with renal disease progression.
These results might contribute to a better knowledge of the FHHNC physiopathology providing with new biomarkers to assess disease progression and, eventually, novel therapeutic targets.