Novel compound heterozygous mutations of <i>CLDN16</i> in a patient with familial hypomagnesemia with hypercalciuria and nephrocalcinosis

García-Castaño, Alejandro; Perdomo‐Ramirez, Ana; Vall-Palomar, Mònica; Ramos-Trujillo, Elena; Madariaga, Leire; Ariceta, Gema; Claverie-Martı́n, Félix

doi:10.1002/mgg3.1475

Cited by 7 publications

(3 citation statements)

References 40 publications

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“…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].…”

Section: Discussionmentioning

confidence: 65%

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

Narang

Shimon

Moore

et al. 2021

Uro

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Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare tubulopathy characterized by renal loss of calcium and magnesium leading to progressive renal failure. The disorder is caused by variants to the tight junction proteins claudin-16 and -19. While rare, this disorder causes a significant burden to patients based on its clinical manifestations of various electrolyte abnormalities, nephrocalcinosis, and early progression to renal failure. In this report we describe the diagnosis of a novel variant of CLDN16 which clinically presented with severe hypomagnesemia, hypocalcemia, nephrocalcinosis, and renal failure.

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Section: Discussionmentioning

confidence: 65%

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

Narang

Shimon

Moore

et al. 2021

Uro

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“…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 .…”

Section: Introductionmentioning

confidence: 99%

“…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 .…”

Section: Introductionmentioning

confidence: 99%

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

Vall-Palomar,

Morata,

Duran

et al. 2023

Preprint

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Inter- and intra-familial phenotypic variability is a common observation in genetic diseases. In this study we have gathered a highly unique patient cohort suffering from an ultra-rare renal disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis, with a deep clinical and genetic characterization. In this cohort, we have previously reported a high phenotypic variability between patients harbouring exactly the same mutation in homozygosis (70% of patients), even between siblings. Patients were stratified at the extremes according to their estimated glomerular filtration rate annual decline and subjected to whole exome sequencing aiming to find candidate phenotype modifier genes. The analysis pipeline applied has allowed us to find, for the first time, 17 putative modifier gene variants associated with a more aggressive renal phenotype. Our results led to a panel of genetic variants in novel candidate modifier genes which will be useful to stratify patients according to their risk of developing renal failure earlier in life and, therefore, direct them to more appropriate and personalized therapeutic options.

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Genetic Mutations in Cell Junction Proteins Associated with Brain Calcification

Yang,

Jiang,

Huang

et al. 2024

Movement Disorders

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Intracerebral calcium deposition, classified into primary familial brain calcification (PFBC) and secondary brain calcification, occurs within the brain parenchyma and vasculature. PFBC manifests with progressive motor decline, dysarthria, and cognitive impairment, with limited treatment options available. Recent research has suggested a link between dysfunction of the blood–brain barrier (BBB) and PFBC, with certain genetic variants potentially affecting neurovascular unit (NVU) function, thereby contributing to BBB integrity disruption and brain calcification. Cell junctions play an indispensable role in maintaining the function of NVUs. The pathogenic mechanisms of PFBC‐causative genes, such as PDGFRB, PDGFB, MYORG, and JAM2, involve NVU disruption. Cell junctions, such as tight junctions, gap junctions, adherens junctions, desmosomes, hemidesmosomes, and focal adhesions, are vital for cell–cell and cell–extracellular matrix connections, maintaining barrier function, cell adhesion, and facilitating ion and metabolite exchange. Several recent studies have highlighted the role of mutations in genes encoding cell junction proteins in the onset and progression of brain calcification and its related phenotypes. This emerging body of research offers a unique perspective for investigating the underlying mechanisms driving brain calcification. In this review, we conducted an examination of the literature reporting on genetic variants in cell junction proteins associated with brain calcification to delineate potential molecular pathways and investigate genotype–phenotype correlations. This approach not only reinforces the rationale for molecular subtyping of brain calcification but also lays the groundwork for the discovery of novel causative genes involved in pathogenesis. © 2024 International Parkinson and Movement Disorder Society.

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

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 7 publications

References 40 publications

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

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

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

Genetic Mutations in Cell Junction Proteins Associated with Brain Calcification

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