Dent Disease Type 2 as a Cause of Focal Segmental Glomerulosclerosis in a 6-Year-Old Boy: A Case Report

Bezdíčka, Martin; Langer, J; Háček, Jaromír; Zieg, Jakub

doi:10.3389/fped.2020.583230

Cited by 3 publications

(3 citation statements)

References 16 publications

(14 reference statements)

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“…A variety of histopathological findings have been reported in renal biopsies from DD1 and DD2 patients. Patients may have normal glomerular and/or tubular compartments or glomerulosclerosis with or without tubular atrophy or interstitial fibrosis [ 17 , 18 ]. In our study, six patients underwent renal biopsy.…”

Section: Discussionmentioning

confidence: 99%

Clinical features and genetic analysis of 15 Chinese children with dent disease

Li,

Yang,

Zang

et al. 2024

Renal Failure

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Objective The clinical characteristics, genetic mutation spectrum, treatment strategies and prognoses of 15 children with Dent disease were retrospectively analyzed to improve pediatricians’ awareness of and attention to this disease. Methods We analyzed the clinical and laboratory data of 15 Chinese children with Dent disease who were diagnosed and treated at our hospital between January 2017 and May 2023 and evaluated the expression of the CLCN5 and OCRL1 genes. Results All 15 patients were male and complained of proteinuria, and the incidence of low-molecular-weight proteinuria (LMWP) was 100.0% in both Dent disease 1 (DD1) and Dent disease 2 (DD2) patients. The incidence of hypercalciuria was 58.3% (7/12) and 66.7% (2/3) in DD1 and DD2 patients, respectively. Nephrocalcinosis and nephrolithiasis were found in 16.7% (2/12) and 8.3% (1/12) of DD1 patients, respectively. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in 1 patient, minimal change lesion in 5 patients, and small focal acute tubular injury in 1 patient. A total of 11 mutations in the CLCN5 gene were detected, including 3 missense mutations (25.0%, c.1756C > T, c.1166T > G, and c.1618G > A), 5 frameshift mutations (41.7%, c.407delT, c.1702_c.1703insC, c.137delC, c.665_666delGGinsC, and c.2200delG), and 3 nonsense mutations (25.0%, c.776G > A, c.1609C > T, and c.1152G > A). There was no significant difference in age or clinical phenotype among patients with different mutation types ( p > 0.05). All three mutations in the OCRL1 gene were missense mutations (c.1477C > T, c.952C > T, and c.198A > G). Conclusion Pediatric Dent disease is often misdiagnosed. Protein electrophoresis and genetic testing can help to provide an early and correct diagnosis.

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Section: Discussionmentioning

confidence: 99%

Clinical features and genetic analysis of 15 Chinese children with dent disease

Li,

Yang,

Zang

et al. 2024

Renal Failure

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“…Reports of HS patients and Dent disease 2 (DD2) suggested that genetic changes in the OCRL1 (inositol polyphosphate-5-phosphatase 1) gene could be predisposing to HS [ 24 ]. OCRL1 is involved in the regulation of membrane trafficking and plays an important role in primary cilium formation; mutations in this gene cause, among other, DD2, a renal disease characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency [ 91 ]. Marzuillo et al [ 24 ] described five DD2 patients, four of whom with concomitant HS and all these patients carried OCRL1 mutations, resulting in significantly reduced inositol polyphosphate-5-phosphatase activity.…”

Section: Genetics Of Hs In the Setting Of Other Diseasesmentioning

confidence: 99%

Hidradenitis Suppurativa: A Perspective on Genetic Factors Involved in the Disease

et al. 2022

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Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease of the pilosebaceous unit, clinically consisting of painful nodules, abscesses, and sinus tracts mostly in, but not limited to, intertriginous skin areas. HS can be defined as a complex skin disease with multifactorial etiologies, including—among others—genetic, immunologic, epigenetic, and environmental factors. Based on genetic heterogeneity and complexity, three different forms can be recognized and considered separately as sporadic, familial, and syndromic. To date, several genetic variants associated to disease susceptibility, disease-onset, and/or treatment response have been reported; some of these reside in genes encoding the gamma-secretase subunits whereas others involve autoinflammatory and/or keratinization genes. The aim of this perspective work is to provide an overview of the contribution of several genetic studies encompassing family linkage analyses, target candidate gene studies, and -omic studies in this field. In our viewpoint, we discuss the role of genetics in Hidradenitis suppurativa considering findings based on Sanger sequencing as well as the more recent Next Generation Sequencing (i.e., exome sequencing or RNA Sequencing) with the aim of better understanding the etio-pathogenesis of the disease as well as identifying novel therapeutic strategies.

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“…Inactivating variants in either gene is responsible for Dent disease in hemizygous males. Dent disease type 2 is allelic with a more severe phenotype called Lowe syndrome which is characterized by ocular abnormalities (prenatal dense congenital cataracts, glaucoma, microphthalmia, decreased visual acuity), neonatal hypotonia, areflexia, and intellectual impairment (Bezdicka, Langer, Hacek, & Zieg, 2020; Hichri et al, 2011). Dent disease type 2 arises from truncating variants in exon 1 through 7 while the Lowe phenotype arises from variants in exons 8 through 24.…”

Section: Overview Of Genetic Causes Of Fsgs/srnsmentioning

confidence: 99%

Monogenic focal segmental glomerulosclerosis: A conceptual framework for identification and management of a heterogeneous disease

Sambharia

Rastogi

Thomas

2022

American J of Med Genetics Pt C

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Focal segmental glomerulosclerosis (FSGS) is not a disease, rather a pattern of histological injury occurring from a variety of causes. The exact pathogenesis has yet to be fully elucidated but is likely varied based on the type of injury and the primary target of that injury. However, the approach to treatment is often based on the degree of podocyte foot process effacement and clinical presentation without sufficient attention paid to etiology. In this regard, there are many monogenic causes of FSGS with variable presentation from nephrotic syndrome with histological features of primary podocytopathy to more modest degrees of proteinuria with limited evidence of podocyte foot process injury. It is likely that genetic causes are largely underdiagnosed, as the role and the timing of genetic testing in FSGS is not established and genetic counseling, testing options, and interpretation of genotype in the context of phenotype may be outside the scope of practice for both nephrologists and geneticists. Yet most clinicians believe that a genetic diagnosis can lead to targeted therapy, limit the use of high-dose corticosteroids as a therapeutic trial, and allow the prediction of the natural history and risk for recurrence in the transplanted kidney. In this manuscript, we emphasize that genetic FSGS is not monolithic in its presentation, opine on the importance of genetic testing and provide an algorithmic approach to deployment of genetic testing in a timely fashion when faced with a patient with FSGS.

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Dent Disease Type 2 as a Cause of Focal Segmental Glomerulosclerosis in a 6-Year-Old Boy: A Case Report

Cited by 3 publications

References 16 publications

Clinical features and genetic analysis of 15 Chinese children with dent disease

Clinical features and genetic analysis of 15 Chinese children with dent disease

Hidradenitis Suppurativa: A Perspective on Genetic Factors Involved in the Disease

Monogenic focal segmental glomerulosclerosis: A conceptual framework for identification and management of a heterogeneous disease

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