Last update 19 Sep 2024

Dent Disease

Last update 19 Sep 2024

Basic Info

Synonyms

Dent Disease, Dent disease, Dent syndrome

+ [17]

Introduction

X-linked recessive NEPHROLITHIASIS characterized by HYPERCALCIURIA; HYPOPHOSPHATEMIA; NEPHROCALCINOSIS; and PROTEINURIA. It is associated with mutations in the voltage-gated chloride channel, CLC-5 (Dent Disease I). Another group of mutations associated with this disease is in phosphatidylinositol 4,5-bisphosphate-5-phosphatase gene.

Clinical Trials associated with Dent Disease

NCT06017193 / Not yet recruitingNot ApplicableIIT

Ultrasonic Imaging of Bone Graft Healing in Extraction Sockets for Precise and Personalized Implant Therapy (HUM00226516)

The design is a single blinded, dual comparative study of ultrasound versus micro-CT/LASCA in one study group. Up to a total of 140 subjects registered will be recruited. Subjects who are treatment planned for extraction of a hopeless tooth and socket augmentation with bone graft and are planned for a dental implant surgery. The socket will be evaluated before the extraction and multi-time points during healing until an implant is placed with various evaluation tools, including ultrasound.

Start Date01 Jun 2024

Sponsor / Collaborator

University of Michigan

[+1]

NCT04459013 / CompletedNot Applicable

Evaluation of the Release of Monomers From Composite Bonding Resins in Orthodontics

In recent decades, the field of public health has become increasingly interested in endocrine disruptors, and their effects on humans. Indeed, various scientific studies have highlighted an evolution in the frequency of pathologies due to these substances, affecting in particular the reproductive organs. Many concerns are expressed about the impact of these substances, present in the environment or in consumer products, on the hormonal system. Effects have been observed in animals in experimental studies, but the question of extrapolating these results to humans arises, especially for exposures at low doses.
In orthodontics, the composite is the material of choice mainly for bonding fasteners, then bonding a compression wire. These composite materials contain many monomers. The polemics launched on Bisphenol A and the questions of our patients on the nature and toxicity of dental products oblige us to reflect on their harmfulness after their placement in the oral cavity. Many questions arise today about dental composites and their participation in the release of endocrine disruptors. Indeed, Bisphenol A is used in the manufacturing process of the monomers of orthodontic composites, as precursors of Bis-GMA and Bis-DMA. The objective of this study is to search for the presence of BPA, TEGDMA, BisGMA, BisDMA and UDMA monomers, and to carry out the samples and their analysis at different clinical times (at T0, after the removal of orthodontic attachments, after the placement of the compression, one hour later, one week later, one month later and 6 months later) and the comparison of this quantification to that without orthodontic restraint. Studies have been performed in vitro, but very little in vivo. In addition, these studies are only carried out on release at the time of installation, but few are interested in the continuation of the phenomenon over time and the deterioration of the composite. Although the short-term toxicity of BPA is low, its dangerousness lies in its potential endocrine disrupting effect and which can induce long-term chronic toxicity.
Compounds such as TEGDMA, BisGMA, BisDMA and UDMA differ greatly in their volatility due to their different chemical structures as well as in their stability in saliva; Many methods have been developed to study each monomer individually or to study them simultaneously using different analytical techniques to determine their presence and to quantify them after their release from dental products. The analysis of the samples is carried out by liquid chromatography (HPLC).

Start Date03 Jun 2020

Sponsor / Collaborator

Assistance Publique des Hôpitaux de Paris SA

NCT04187053 / CompletedPhase 4IIT

Clinical and Microbiologic Outcomes of Adjunctive Antimicrobial Photodynamic Therapy in the Non-surgical Treatment of Peri-implant Disease

The purpose of this study is to compare clinical outcomes (change in bleeding sites (BOP) and probing depth reduction (PPD) after mechanical debridement of implant surfaces at sites exhibiting plaque induced inflammation with or without adjunctive antimicrobial photodynamic therapy (aPDT) and assess the microbiologic profile of plaque samples before and after treatment with or without aPDT samples.

Start Date14 Feb 2020

Sponsor / Collaborator

University of Texas Health Science Center at Houston

100 Clinical Results associated with Dent Disease

100 Translational Medicine associated with Dent Disease

0 Patents (Medical) associated with Dent Disease

434

Literatures (Medical) associated with Dent Disease

24 Jan 2024·BMC medical genomics

Prenatal diagnosis of dent disease type I with a nonsense pathogenic variant in CLCN5: a case study.

Article

Author: Ruijue Zhu ; Mingming Zhu ; Boye Wang ; Enen Chen ; Danlei Cai ; Yinghong Yang ; Yi Liang ; Chuqi Su ; Ding Wang ; Xiaofang Sun ; Linhuan Huang ; Yingjun Xie

INTRODUCTION:

Dent disease type I is a rare X-linked recessive renal tubular disease resulting from pathogenic variants in the CLCN5 gene. Due to the rarity of Dent disease type I and the diversity of its phenotypes, its clinical diagnosis is complex and poses a challenge to clinicians.

METHODS:

A foetus and a child from a 36-year-old pregnant woman with a birth history of abnormal children were enrolled in this study. Pregnant women undergo amniocentesis for prenatal diagnosis at the gestational age of 12^+ 3 weeks. Chromosomal microarray (CMA) analysis and whole-exome sequencing (WES) were employed to investigate the chromosomal copy number and single gene variants. Literature retrieval and data analysis were performed for genotype and phenotype collection analysis.

RESULTS:

No chromosomal abnormalities or CNVs were detected in the entire family through karyotype and familial CMA analyses. WES identified a nonsense pathogenic variant in CLCN5 of the X chromosome, c.1942 C > T (exon 11, NM_000084), which was inherited from his mother, who exhibited regular clinical features.

CONCLUSION:

This study suggests that children with low-molecular-weight proteinuria and hypercalciuria should undergo prompt genetic testing to exclude Dent disease.

17 Nov 2023·Biomedicines

Characterization of pre-mRNA Splicing Defects Caused by CLCN5 and OCRL Mutations and Identification of Novel Variants Associated with Dent Disease.

Article

Author: Glorián Mura-Escorche ; Ana Perdomo-Ramírez ; Elena Ramos-Trujillo ; Carmen Jane Trujillo-Frías ; Félix Claverie-Martín ; RenalTube Group

Dent disease (DD) is an X-linked renal tubulopathy characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis and progressive renal failure. Two-thirds of cases are associated with inactivating variants in the CLCN5 gene (Dent disease 1, DD1) and a few present variants in the OCRL gene (Dent disease 2, DD2). The aim of the present study was to test the effect on the pre-mRNA splicing process of DD variants, described here or in the literature, and describe the clinical and genotypic features of thirteen unrelated patients with suspected DD. All patients presented tubular proteinuria, ten presented hypercalciuria and five had nephrolithiasis or nephrocalcinosis. CLCN5 and OCRL genes were analyzed by Sanger sequencing. Nine patients showed variants in CLCN5 and four in OCRL; eight of these were new. Bioinformatics tools were used to select fifteen variants with a potential effect on pre-mRNA splicing from our patients' group and from the literature, and were experimentally tested using minigene assays. Results showed that three exonic missense mutations and two intronic variants affect the mRNA splicing process. Our findings widen the genotypic spectrum of DD and provide insight into the impact of variants causing DD.

28 Aug 2023·BMC nephrology

A novel likely pathogenic CLCN5 variant in Dent's disease.

Article

Author: S Hayward ; J Norton ; L Bownass ; C Platt ; Genomics England Research Consortium ; H Campbell ; E Watson ; N Forrester ; S Smithson ; A Menon

BACKGROUND:

The majority of cases of Dent's disease are caused by pathogenic variants in the CLCN5 gene, which encodes a voltage-gated chloride ion channel (ClC-5), resulting in proximal tubular dysfunction. We present three members of the same family and one unrelated paediatric patient with the same insertion-deletion CLCN5 variant. The identification of these patients and positive familial segregation led to the re-classification of this variant from one of unknown significance to one of likely pathogenicity.

CASE PRESENTATION:

A 41 year old male presented with end stage kidney failure, proteinuria and haematuria. Whole genome sequencing identified an insertion-deletion variant in CLCN5, resulting in a missense change (c.1744_1745delinsAA p.(Ala582Lys)). His brother and nephew, who both exhibited renal impairment, haematuria, proteinuria, glycosuria and nephrocalcinosis, were found to have the same variant. In addition, genetic testing of an unrelated paediatric patient who presented with proteinuria and hypercalciuria, demonstrated the same variant.

CONCLUSIONS:

The identification of this novel variant in four individuals with features of Dent's disease, has led to the re-classification of the variant to one of likely pathogenicity. As a result, our patients and any future patients with the same variant can be offered a likely diagnosis, without the need for kidney biopsy, and their family members can be offered genetic screening.

News (Medical) associated with Dent Disease

08 Nov 2022

·www.biospace.com

Sentynl Therapeutics Recognizes Menkes Disease Awareness Month, Committed to the Development of Tests for Early Diagnosis of Patients with Menkes Disease

SAN DIEGO and CALIFORNIA, Md., Nov. 8, 2022 /PRNewswire/ -- Sentynl Therapeutics, Inc. ("Sentynl") a US-based biopharmaceutical company focused on bringing innovative therapies to patients living with rare disease, joins the global Menkes disease community including the Menkes Foundation ("Menkes Foundation") in recognizing the month of November as Menkes Disease Awareness Month. In support of patients and families affected by this devastating and fatal disease, Sentynl is collaborating with researchers at a world-leading academic medical center to develop and validate a novel laboratory test that could potentially diagnose Menkes disease at birth. "It is our aspiration that a test for Menkes disease will be integrated into every state's Newborn Screening Program to aid in the early diagnosis of patients who might otherwise be missed," stated Matt Heck, Sentynl's Chief Executive Officer. Sentynl Therapeutics Recognizes Menkes Disease Awareness Month, Supports Development of Tests For Early Diagnosis Today, most patients with Menkes disease are misdiagnosed or diagnosed late after irreversible neurodevelopmental damage has occurred. Over the last year, Sentynl has been advocating for the inclusion of the ATP7A gene in commercially-available genetic panels. Sentynl is also proud to support initiatives like BeginNGS, a Rady Children's Institute for Genomic Medicine led pilot, with the goal of leveraging rapid whole genome sequencing (rWGS) to significantly improve identification of pediatric genetic disorders. Drew and Jamie Eckman, Founders of the Menkes Foundation stated that "the work Sentynl is spearheading to advance available and early genetic testing for suspected patients with Menkes disease is what the community has desperately needed. The development of this test represents a key milestone in the fight against Menkes disease and to see it incorporated into newborn screening will be an incredible achievement that will save lives. We are thrilled to partner with Sentynl Therapeutics in promoting awareness of Menkes disease." About Menkes Disease Menkes disease is a rare X-linked recessive pediatric disease caused by gene mutations of the copper transporter ATP7A. The minimum birth prevalence for Menkes disease is believed to be 1 in 34,810 live male births, and potentially as high as 1 in 8,664 live male births, based on recent genome-based ascertainment (Kaler SG, Ferreira CR, Yam LS. Estimated birth prevalence of Menkes disease and ATP7Arelated disorders based on the Genome Aggregation Database (gnomAD). Molecular Genetics and Metabolism Reports 2020 June 5;24:100602). The condition is characterized by distinctive clinical features, including sparse and depigmented hair ("kinky hair"), connective tissue problems, and severe neurological symptoms such as seizures, hypotonia, failure to thrive, and neurodevelopmental delays. Mortality is high in untreated Menkes disease, with many patients dying before the age of three years old. Milder versions of ATP7A mutations are associated with other conditions, including Occipital Horn Syndrome and ATP7A-related Distal Motor Neuropathy. Currently, there is no FDA-approved treatment for Menkes disease and its variants. About Sentynl Therapeutics Sentynl Therapeutics is a US-based biopharmaceutical company focused on bringing innovative therapies to patients living with rare diseases. The company was acquired by the Zydus Group in 2017. Sentynl's experienced management team has previously built multiple successful pharmaceutical companies. With a focus on commercialization, Sentynl looks to source effective and well differentiated products across a broad spectrum of therapeutic areas to address unmet needs. Sentynl is committed to the highest ethical standards and compliance with all applicable laws, regulations, and industry guidelines. For more information, visit . About the Menkes Foundation For more information about the Menkes Foundation, please visit . Contacts: Michael Hercz Sentynl Therapeutics, Inc. ir@sentynl.com Jamie Eckman The Menkes Foundation info@themenkesfoundation.org

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