Focal Segmental Membranoproliferative Glomerulonephritis: A Histological Variant of Denys-Drash Syndrome.

Karmila, A B; Yap, Yok Chin; Appadurai, Mirunalini; Oh, Lixian; M, Fazarina; Ghani, Fauzah Abd; Ariffin, Hany

doi:10.1080/15513815.2019.1686788

Cited by 1 publication

(5 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mutational survey of WT1 in steroid-resistant nephrotic syndrome cohorts [2,3] revealed that an intron 9 splice mutation typically causes FSGS with a gonadal tumor, whereas missense and truncating mutations result in DMS with nephroblastoma. However, morphologic abnormalities considerably vary in histologic appearance among individuals with DDS/FS [3][4][5][6][7][8][9]. Detailed analysis of the renal histology of DDS individuals revealed complex glomerular changes, including endotheliosis-like endothelial injuries, foot-process fusion, and GBM alterations [6].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies report a significant fraction of DDS/FS individuals, including original and some familial cases, display MPGN with IC deposition in addition to FSGS or DMS, a histopathology commonly seen in WT1-related glomerulopathy [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] (Tables 1 and 2). Out of six DDS cases, four patients harbored a p.Arg467Trp (NM_024426.6:c.1399C > T) variant [4][5][6], the most common substitution (present in 40% of DDS patients), and two harbored a nonsense p.Arg463Ter (NM_024426.6:c.1387C > T) variant [3,7] manifesting in an MPGN pattern. Moreover, nine FS cases have been reported, including two monozygous twins harboring a donor splice site mutation in intron 9 and initially presenting with MPGN [8,9].…”

Section: Discussionmentioning

confidence: 99%

“…In this context, it is plausible that ICs might form through aberrant immune responses against oncofetal and/or non-autologous tumor antigens and trigger endothelial injuries of glomerular capillaries in WT patients [23]. Clinically, in most DDS cases, glomerulonephritis precedes or manifests simultaneously with WT diagnosis [3][4][5][6][7][12][13][14][15][16] (Tables 1 and 2). Moreover, nephrotic syndrome can persist, even after complete excision of tumors with no evidence of recurrence and metastasis [4,7].…”

Section: Discussionmentioning

confidence: 99%

“…4 Department of Pathology, Aizawa Hospital, Matsumoto, Japan. 5 Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Japan. 6 Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.…”

Section: Supplementary Informationmentioning

confidence: 99%

“…WT1-related nephropathy is generally ascribed to developmental defects in glomerular podocytes [2,3]. Several patients with DDS or FS display membranoproliferative glomerulonephritis (MPGN) that is mainly characterized by subendothelial immune deposits [3][4][5][6][7][8][9], suggesting that renal pathologies resulting from WT1 mutations are complex and affected by multiple factors. Possible pathogenic mechanisms are discussed by reviewing the current literature.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Immune-complex glomerulonephritis with a membranoproliferative pattern in Frasier syndrome: a case report and review of the literature

et al. 2020

View full text Add to dashboard Cite

Background: Mutations in the Wilms tumor 1 gene cause a spectrum of podocytopathy ranging from diffuse mesangial sclerosis to focal segmental glomerulosclerosis. In a considerable fraction of patients with Wilms tumor 1 mutations, the distinctive histology of immune-complex-type glomerulonephritis has been reported. However, the clinical relevance and etiologic mechanisms remain unknown. Case presentation: A 5-year-old child presented with steroid-resistant nephrotic range proteinuria. Initial renal biopsy revealed predominant diffuse mesangial proliferation with a double-contour and coexisting milder changes of focal segmental glomerulosclerosis. Immunofluorescence and electron microscopy revealed a full-house-pattern deposition of immune complexes in the subendothelial and paramesangial areas. Serial biopsies at 6 and 8 years of age revealed that more remarkable changes of focal segmental glomerulosclerosis had developed on top of the initial proliferative glomerulonephritis. Identification of a de novo Wilms tumor 1 splice donor-site mutation in intron 9 (NM_024426.6:c.1447 + 4C > T) and 46,XY-gonadal dysgenesis led to the diagnosis of Frasier syndrome. Conclusions: Our findings, together with those of others, point to the importance of heterogeneity in clinicopathological phenotypes caused by Wilms tumor 1 mutations and suggest that immune-complex-mediated membranoproliferative glomerulopathy should be considered as a histological variant.

show abstract