Novel compound heterozygous mutations of CLDN16 in a patient with familial hypomagnesemia with hypercalciuria and nephrocalcinosis
Abstract Background Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive tubulopathy characterized by excessive urinary wasting of magnesium and calcium, bilateral nephrocalcinosis, and progressive chronic renal failure in childhood or adolescence. FHHNC...
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doaj-bceb1a725ee9429f978d8a8b1efc301d2020-11-25T04:09:44ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-11-01811n/an/a10.1002/mgg3.1475Novel compound heterozygous mutations of CLDN16 in a patient with familial hypomagnesemia with hypercalciuria and nephrocalcinosisAlejandro García‐Castaño0Ana Perdomo‐Ramirez1Mònica Vall‐Palomar2Elena Ramos‐Trujillo3Leire Madariaga4Gema Ariceta5Felix Claverie‐Martin6Biocruces Bizkaia Research Institute Barakaldo Bizkaia SpainUnidad de Investigación Hospital Universitario Nuestra Señora de Candelaria Santa Cruz de Tenerife SpainFisiopatologia Renal Centro de Investigaciones en Bioquímica y Biología Molecular (CIBBIM) Vall d’Hebron Institut de Recerca (VHIR Barcelona SpainUnidad de Investigación Hospital Universitario Nuestra Señora de Candelaria Santa Cruz de Tenerife SpainBiocruces Bizkaia Research Institute Barakaldo Bizkaia SpainFisiopatologia Renal Centro de Investigaciones en Bioquímica y Biología Molecular (CIBBIM) Vall d’Hebron Institut de Recerca (VHIR Barcelona SpainUnidad de Investigación Hospital Universitario Nuestra Señora de Candelaria Santa Cruz de Tenerife SpainAbstract Background Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive tubulopathy characterized by excessive urinary wasting of magnesium and calcium, bilateral nephrocalcinosis, and progressive chronic renal failure in childhood or adolescence. FHHNC is caused by mutations in CLDN16 and CLDN19, which encode the tight‐junction proteins claudin‐16 and claudin‐19, respectively. Most of these mutations are missense mutations and large deletions are rare. Methods We examined the clinical and biochemical features of a Spanish boy with early onset of FHHNC symptoms. Exons and flanking intronic segments of CLDN16 and CLDN19 were analyzed by direct sequencing. We developed a new assay based on Quantitative Multiplex PCR of Short Fluorescent Fragments (QMPSF) to investigate large CLDN16 deletions. Results Genetic analysis revealed two novel compound heterozygous mutations of CLDN16, comprising a missense mutation, c.277G>A; p.(Ala93Thr), in one allele, and a gross deletion that lacked exons 4 and 5,c.(840+25_?)del, in the other allele. The patient inherited these variants from his mother and father, respectively. Conclusions Using direct sequencing and our QMPSF assay, we identified the genetic cause of FHHNC in our patient. This QMPSF assay should facilitate the genetic diagnosis of FHHNC. Our study provided additional data on the genotypic spectrum of the CLDN16 gene.https://doi.org/10.1002/mgg3.1475claudin‐16CLDN16deletionhypomagnesemianovel mutationsQMPSF |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alejandro García‐Castaño Ana Perdomo‐Ramirez Mònica Vall‐Palomar Elena Ramos‐Trujillo Leire Madariaga Gema Ariceta Felix Claverie‐Martin |
spellingShingle |
Alejandro García‐Castaño Ana Perdomo‐Ramirez Mònica Vall‐Palomar Elena Ramos‐Trujillo Leire Madariaga Gema Ariceta Felix Claverie‐Martin Novel compound heterozygous mutations of CLDN16 in a patient with familial hypomagnesemia with hypercalciuria and nephrocalcinosis Molecular Genetics & Genomic Medicine claudin‐16 CLDN16 deletion hypomagnesemia novel mutations QMPSF |
author_facet |
Alejandro García‐Castaño Ana Perdomo‐Ramirez Mònica Vall‐Palomar Elena Ramos‐Trujillo Leire Madariaga Gema Ariceta Felix Claverie‐Martin |
author_sort |
Alejandro García‐Castaño |
title |
Novel compound heterozygous mutations of CLDN16 in a patient with familial hypomagnesemia with hypercalciuria and nephrocalcinosis |
title_short |
Novel compound heterozygous mutations of CLDN16 in a patient with familial hypomagnesemia with hypercalciuria and nephrocalcinosis |
title_full |
Novel compound heterozygous mutations of CLDN16 in a patient with familial hypomagnesemia with hypercalciuria and nephrocalcinosis |
title_fullStr |
Novel compound heterozygous mutations of CLDN16 in a patient with familial hypomagnesemia with hypercalciuria and nephrocalcinosis |
title_full_unstemmed |
Novel compound heterozygous mutations of CLDN16 in a patient with familial hypomagnesemia with hypercalciuria and nephrocalcinosis |
title_sort |
novel compound heterozygous mutations of cldn16 in a patient with familial hypomagnesemia with hypercalciuria and nephrocalcinosis |
publisher |
Wiley |
series |
Molecular Genetics & Genomic Medicine |
issn |
2324-9269 |
publishDate |
2020-11-01 |
description |
Abstract Background Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive tubulopathy characterized by excessive urinary wasting of magnesium and calcium, bilateral nephrocalcinosis, and progressive chronic renal failure in childhood or adolescence. FHHNC is caused by mutations in CLDN16 and CLDN19, which encode the tight‐junction proteins claudin‐16 and claudin‐19, respectively. Most of these mutations are missense mutations and large deletions are rare. Methods We examined the clinical and biochemical features of a Spanish boy with early onset of FHHNC symptoms. Exons and flanking intronic segments of CLDN16 and CLDN19 were analyzed by direct sequencing. We developed a new assay based on Quantitative Multiplex PCR of Short Fluorescent Fragments (QMPSF) to investigate large CLDN16 deletions. Results Genetic analysis revealed two novel compound heterozygous mutations of CLDN16, comprising a missense mutation, c.277G>A; p.(Ala93Thr), in one allele, and a gross deletion that lacked exons 4 and 5,c.(840+25_?)del, in the other allele. The patient inherited these variants from his mother and father, respectively. Conclusions Using direct sequencing and our QMPSF assay, we identified the genetic cause of FHHNC in our patient. This QMPSF assay should facilitate the genetic diagnosis of FHHNC. Our study provided additional data on the genotypic spectrum of the CLDN16 gene. |
topic |
claudin‐16 CLDN16 deletion hypomagnesemia novel mutations QMPSF |
url |
https://doi.org/10.1002/mgg3.1475 |
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