Identification of modifier gene variants overrepresented in familial hypomagnesemia with hypercalciuria and nephrocalcinosis patients with a more aggressive renal phenotype.

ABSTRACT: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an ultra-rare autosomal recessive renal tubular disease with an incidence of <1/1.000.000 individuals, caused by loss-of-function mutations in CLDN16 and CLDN19. Our study includes a unique cohort representing all known FHHNC patients in Spain, with 90% harbouring mutations in CLDN19. Of these, 70% carry the p.G20D mutation in homozygosis. Despite this high genetic homogeneity, our FHHNC cohort display a high phenotypic variability, even among siblings harbouring identical mutations. Patients were stratified at the extremes of the renal phenotype according to their estimated glomerular filtration rate annual decline and subjected to whole exome sequencing (WES) aiming to find candidate phenotype-modifier genes. Ini

SUBMITTER: Vall-Palomar M 

PROVIDER: S-EPMC12005529 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature