Renal, Ocular, and Neuromuscular Involvements in Patients with CLDN19 Mutations

Faguer, Stanislas; Chauveau, Dominique; Pascal, Pierre; Tack, Ivan; Cointault, Olivier; Rostaing, Lionel; Vargas‐Poussou, Rosa; Ribes, David

doi:10.2215/cjn.02870310

Cited by 29 publications

(22 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Knockdown of claudin-19 by small interfering RNA abolishes the transepithelial electrical resistance, showing the importance of this protein in the permeability characteristics of this epithelium (28). Neurologic manifestations were previously described in two patients with CLDN19 mutations included in this study (12). Extrarenal symptoms may be accounted for by the expression in other tissues of claudin-19 described in the Cldn19-null mouse, which presents peripheral nervous system deficits caused by the absence of claudin-19 in the tight junction of the Schwann cells of peripheral myelinated axons (29).…”

Section: Discussionsupporting

confidence: 51%

“…Neurologic manifestations, mainly exercise intolerance with electromyological alteration, were present in two previously described patients (12). Electrophysiological studies were not systematically carried out for the patients without clinical manifestations.…”

Section: Clinical and Biologic Follow-upmentioning

confidence: 98%

“…Genomic DNA was extracted by standard methods from peripheral blood samples after written informed consent had been obtained from the patients or their parents. Mutation analysis was performed based on PCR amplification followed by sequencing as described (11,12) Quantitative Multiplex PCR for Short Fluorescent Fragments. We adapted the quantitative multiplex PCR for short fluorescent fragments (QMPSF) method (13) for the detection of large rearrangements of the CLDN19 gene for patients with homozygous mutations and no history of consanguinity for whom parental DNA was not available.…”

Section: Genetic Studiesmentioning

confidence: 99%

See 2 more Smart Citations

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

Godron¹,

Harambat²,

Boccio³

et al. 2012

Clinical Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

SummaryBackground and objectives Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a rare autosomal recessive renal tubular disease. It is caused by mutations in CLDN16 and CLDN19, encoding claudin-16 and -19, respectively. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is usually complicated by progressive CKD. The objectives of this study were to describe the clinical and genetic features of familial hypomagnesemia with hypercalciuria and nephrocalcinosis and analyze phenotype-genotype associations in patients with CLDN16 or CLDN19 mutations.Design, setting, participants, & measurements Data from 32 genetically confirmed patients (9 patients with CLDN16 and 23 patients with CLDN19 mutations) from 26 unrelated families were retrospectively reviewed.Results Diagnosis was based on clinical criteria at a median age of 9.5 years and confirmed by genetic testing at a median age of 15.5 years. In total, 13 CLDN16 or CLDN19 mutations were identified, including 8 novel mutations. A founder effect was detected for the recurrent CLDN16 p.Ala139Val mutation in North African families and the CLDN19 p.Gly20Asp mutation in Spanish and French families. CKD was more frequently observed in patients with CLDN19 mutations: survival without CKD or ESRD was 56% at 20 years of age in CLDN19 versus 100% in CLDN16 mutations (log rank P,0.01). Ocular abnormalities were observed in 91% of patients with CLDN19 mutations and none of the patients with CLDN16 mutations (P,0.01). Treatments seem to have no effect on hypercalciuria and CKD progression.Conclusions Patients with CLDN19 mutations may display more severe renal impairment than patients with CLDN16 mutations. Ocular abnormalities were observed only in patients with CLDN19 mutations.

show abstract

Section: Discussionsupporting

confidence: 51%

Section: Clinical and Biologic Follow-upmentioning

confidence: 98%

Section: Genetic Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

Godron¹,

Harambat²,

Boccio³

et al. 2012

Clinical Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

show abstract

“…These data expand the FHHNC phenotype, which classically includes hypomagnesaemia, hypercalciuria and nephrocalcinosis. As claudin-19 is expressed in the retinal epithelium,31 ophthalmic diseases can also be found in patients with CLDN19 mutations 30 31 52 53. In this study, two patients presented only mild enamel defects and a severe ocular phenotype including myopia, retinopathy and strabismus.…”

Section: Discussionmentioning

confidence: 55%

Amelogenesis imperfecta in familial hypomagnesaemia and hypercalciuria with nephrocalcinosis caused byCLDN19gene mutations

et al. 2016

Self Cite

View full text Add to dashboard Cite

For the first time, it was demonstrated that AI is associated with FHHNC in patients carrying CLDN19 mutations. The data suggest claudin-19 as an additional determinant in enamel formation. Indeed, the coexistence of hypoplastic and hypomineralised AI in the patients was consistent with claudin-19 expression in both secretory and maturation stages. Additional indirect systemic effects cannot be excluded.

show abstract

“…The identified mutation (G130D) replaces a neutral with a negatively charged amino acid located in the third TMD of claudin-19 protein. Six different mutations have been reported in the CLDN19 gene so far [9,10,23,24]. The mutations, G20D and P28L lie in the first TMD; V44M and Q57E lie in the first extracellular loop; L90P lies in the second TMD, and G123R lies in the third TMD of the protein.…”

Section: Discussionmentioning

confidence: 99%

Mutation in the Tight-Junction Gene Claudin 19 <i>(CLDN19)</i> and Familial Hypomagnesemia, Hypercalciuria, Nephrocalcinosis (FHHNC) and Severe Ocular Disease

Naeem

Hussain²,

Akhtar³

2011

Am J Nephrol

View full text Add to dashboard Cite

Background/Aims: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare renal tubular disorder complicated by progressive renal failure during childhood or adolescence. Recently, causative mutations in the CLDN19 gene have been identified in FHHNC patients presenting with severe ocular involvement. The aim of the study was to investigate the molecular genetic defect underlying FHHNC in a consanguineous Pakistani family. Methods: Clinical and biochemical parameters of the proband were studied during the follow-up period over 5 years. Genotyping of 7 members of the family was performed by amplifying microsatellite markers, tightly linked to the CLDN16 and CLDN19 genes. The two genes were sequenced directly in an automated sequencer. PCR-RFLP assay and bioinformatic analysis were performed to verify the identified mutation. Results: Genotyping revealed that the proband was homozygous for the marker loci tightly linked to the CLDN19 gene. Sequence analysis in the proband revealed homozygosity for a novel missense mutation in exon 3 of the CLDN19 gene (389G>A) resulting in G130D amino acid substitution. Bioinformatic analysis supported the pathogenicity of the identified mutation. Family screening revealed nephrolithiasis in 3 of 6 (50%) heterozygous carriers of the pathogenic mutation. Conclusion: This study supports the fundamental role of claudin 19 for magnesium homeostasis, normal tubular structures in the kidney, and undisturbed organization and development of the retina.

show abstract

Renal, Ocular, and Neuromuscular Involvements in Patients with CLDN19 Mutations

Cited by 29 publications

References 25 publications

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

Amelogenesis imperfecta in familial hypomagnesaemia and hypercalciuria with nephrocalcinosis caused byCLDN19gene mutations

Mutation in the Tight-Junction Gene Claudin 19 <i>(CLDN19)</i> and Familial Hypomagnesemia, Hypercalciuria, Nephrocalcinosis (FHHNC) and Severe Ocular Disease

Contact Info

Product

Resources

About