Novel compound heterozygous mutations of CLDN16 in a patient with familial hypomagnesemia with hypercalciuria and nephrocalcinosis

Abstract

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Novel Variant in CLDN16: A Further Step in the Diagnosis of Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis—A Case Report

“…The etiology for renal deterioration in FHHNC patients has not been elucidated. Possible explanations include the effects of prolonged nephrocalcinosis, inflammation secondary to crystal nephropathy or renal dysplasia due to defective claudin-16 function [14,17,18]. The patient reported here has had a protracted decline which may be explained by a partial loss of function mutation, as prior studies have noted a more rapid decline when complete loss of function is seen [8].…”

Identification of Modifier Gene Variants Overrepresented in Familial Hypomagnesemia With Hypercalciuria and Nephrocalcinosis Patients With a More Aggressive Renal Phenotype

“…Major research efforts in the last decade have been directed towards identifying novel mutations in FHHNC patients 7 and, as a result, 73 and 24 different mutations in CLDN16 and CLDN19 , respectively, have been described and annotated in the Human Gene Mutation Database (HGMD) 8 . Most FHHNC patients have been found to carry CLDN16 mutations, although in the South of Europe (mainly Spain and France) CLDN19 mutations are more prevalent and a specific CLDN19 so-called Hispanic founder mutation (c.59G>A; p.G20D) has been described 9,10 .…”

“…Kidney replacement therapy remains the only curative option in end-stage renal disease patients and renal transplant is usually required during the second to third decades of life 1,2 , causing a severe impairment on quality of life of patients from a very young age. Major research efforts in the last decade have been directed towards identifying novel mutations in FHHNC patients 7 and, as a result, 73 and 24 different mutations in CLDN16 and CLDN19, respectively, have been described and annotated in the Human Gene Mutation Database (HGMD) 8 . Most FHHNC patients have been found to carry CLDN16 mutations, although in the South of Europe (mainly Spain and France) CLDN19 mutations are more prevalent and a specific CLDN19 so-called Hispanic founder mutation (c.59G>A; p.G20D) has been described 9,10 .…”