Truncating Mutations in the Chloride/Proton &lt;i&gt;ClC-5&lt;/i&gt; Antiporter Gene in Seven Jewish Israeli Families with Dent’s 1 Disease

Dinour, Dganit; Davidovitz, Miriam; Levin-Iaina, Nomy; Lotan, Danny; Cleper, Roxana; Weissman, Irith; Knecht, Aaron; Holtzman, Eliezer J.

doi:10.1159/000224793

Cited by 11 publications

(4 citation statements)

References 45 publications

(35 reference statements)

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“…Although Dent disease is often listed as a cause of FS, its prevalence in patients with Dent disease, in whom FS has been described in few cases, is not known. 5,6 Female carriers may have a mild phenotype, including LMWP and hypercalciuria, with nephrocalcinosis or chronic renal failure developing only in very rare cases. 7,8 Dent disease is genetically heterogeneous: 60 % of patients harbor an inactivating mutation of the chloride channel-gated 5 gene (CLCN5) (Dent-1, Online Mendelian Inheritance in Man 300009), 9 15% have inactivating mutations of the inositol polyphosphate-5-phosphatase gene (OCRL) (Dent-2, Online Mendelian Inheritance in Man 300355), [10][11][12] and 25% have no mutation of these genes.…”

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confidence: 99%

Observations of a large Dent disease cohort

Blanchard

Curis

Guyon-Roger

et al. 2016

Kidney International

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Dent disease classically combines low-molecular-weight proteinuria, hypercalciuria with nephrocalcinosis, and renal failure. Nephrotic range proteinuria, normal calciuria, and hypokalemia have been rarely reported. It is unknown whether the changes in phenotype observed over time are explained by a decrease in glomerular filtration rate (GFR) or whether there is any phenotype-genotype relationship. To answer this we retrospectively analyzed data from 109 male patients with CLCN5 mutations (Dent-1) and 9 patients with mutation of the OCRL gene (Dent-2). In Dent-1 disease, the estimated GFR decreased with age, by 1.0 to 1.6 ml/min per 1.73 m(2)/yr in the absence and presence of nephrocalcinosis, respectively, with no significant difference. Median values of low-molecular-weight proteinuria were in the nephrotic range and remained at the same level even in late renal disease. End-stage renal disease occurred in 12 patients, at a median age of 40 years. Hypercalciuria decreased with glomerular filtration and was absent in 40% of the patients under 30 and 85% of those over the age of 30. Hypophosphatemia did not resolve with age and calcitriol concentrations were in the upper normal range. Kalemia decreased with age, with half of the patients over the age of 18 presenting with hypokalemia. Thus, no phenotype/genotype correlation was observed in this cohort of patients with Dent disease.

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confidence: 99%

Observations of a large Dent disease cohort

Blanchard

Curis

Guyon-Roger

et al. 2016

Kidney International

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“…The accurate relationship between genotypes and clinical phenotypes has not been discovered. For example, within one family, the phenotype of the same mutation is not identical, with some presenting with severe kidney stones in infancy, while others may only present with mild LWMP or even normal laboratory findings ( 12 , 13 ). In this case, both the proband and his cousin were absent of nephrocalcinosis at onset, while the proband, not his cousin, developed it during subsequent follow-up.…”

Section: Discussionmentioning

confidence: 99%

A novel CLCN5 frame shift mutation responsible for Dent disease 1: Case report

Zhu

Lin

et al. 2022

Front. Pediatr.

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BackgroundDent disease is a group of inherited X-linked recessive renal tubular disorders. This group of disorders is characterized by low molecular weight proteinuria (LMWP), nephrocalcinosis, hypercalciuria and renal failure.Case presentationHere we report one 11-year-old Chinese boy (proband) and one 13-year-old Chinese boy who was proband's cousin, both presented with massive proteinuria. Further laboratory examinations revealed a lack of nephrocalcinosis, nor any other signs of tubular dysfunction, but only LMWP and hypercalciuria. There was no abnormality in growth, renal function or mineral density of the bones. A novel deletion (c.1448delG) in the CLCN5 gene was identified, resulting in a frame shift mutation (p.Gly483fs). The proband's and his cousin's mothers were found to be the carrier of this mutation.ConclusionsIn this study, we have found a novel frameshift mutation (c. 1448delG) at exon 11 of the CLCN5 gene which leads to Dent disease 1, expanding the spectrum of CLCN5 mutations.

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“…The most common symptom of Dent’s disease is proteinuria, hypercalciuria, nephrocalcinosis, and nephrolithiasis which the latter symptom may cause hematuria in patients. Most affected men suffer from end-stage renal disease, ESRD, in early adulthood [2]. It is worth mentioning that Dent’s disease is very unlikely to be diagnosed in people with mild symptoms especially because of its common features with other kidney disorders [3].…”

Section: Introductionmentioning

confidence: 99%

A Study on the CLCN5 Gene in Iranian Patients: A Report of Novel and Recurrent Mutations

Mollataheri¹,

Mojbafan²,

Hosseini³

et al. 2023

Nephron

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Introduction: Dent’s disease is an X-linked inherited renal tubular disorder characterized by proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, rickets, and end-stage renal disease. Almost 60% of patients have causative mutations in the CLCN5 gene (Dent 1), and 15% of affected individuals have mutations in the OCRL1 gene (Dent 2). The aims of this study are to identify CLCN5 mutations in Iranian families with Dent’s disease and to characterize the associated clinical syndromes. Methods: We studied 14 patients from 13 unrelated Iranian families with a clinical diagnosis of Dent’s disease. Proteinuria was detected in all patients. Nephrolithiasis was found in 5 patient, and hematuria in 2 patients. Most of the affected individuals had nephrocalcinosis. PCR-sequencing for the CLCN5 gene was performed in all 14 patients. Next-generation sequencing (NGS) has also been performed in one patient who we did not find causative mutation. Results: We identified four different CLCN5 mutations including one missense mutation (c.731C>T), one nonsense mutation (c.100C>T), and two novel mutations, consisting of one frameshift mutation (c.1241_1242dupAA) and one splicing mutation (c.805-2A>G). We also identified one OCRL1 mutation, one splicing mutation (c.1466 + 1G>A), using NGS. Conclusion: This is the first report to characterize mutations in the CLCN5 gene in Iranian patients with Dent’s disease and expands the spectrum of CLCN5 mutations by reporting two novel mutations, c.1241_1242dupAA and c.805-2A>G.

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Truncating Mutations in the Chloride/Proton <i>ClC-5</i> Antiporter Gene in Seven Jewish Israeli Families with Dent’s 1 Disease

Cited by 11 publications

References 45 publications

Observations of a large Dent disease cohort

Observations of a large Dent disease cohort

A novel CLCN5 frame shift mutation responsible for Dent disease 1: Case report

A Study on the CLCN5 Gene in Iranian Patients: A Report of Novel and Recurrent Mutations

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