Immune-complex glomerulonephritis with a membranoproliferative pattern in Frasier syndrome: a case report and review of
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CASE REPORT
Open Access
Immune-complex glomerulonephritis with a membranoproliferative pattern in Frasier syndrome: a case report and review of the literature Daisuke Matsuoka1† , Shunsuke Noda1,2†, Motoko Kamiya1,3, Yoshihiko Hidaka1, Hisashi Shimojo4, Yasushi Yamada5, Tsutomu Miyamoto5, Kandai Nozu6, Kazumoto Iijima6 and Hiroyasu Tsukaguchi7*
Abstract 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. Keywords: Focal segmental glomerulosclerosis, Frasier syndrome, Membranoproliferative glomerulonephritis, Wilms tumor
Background Mutations in Wilms tumor 1 (WT1) gene cause several diseases characterized by renal and /or genital anomalies, such as Denys–Drash syndrome (DDS), Frasier syndrome (FS), and isolated focal segmental glomerulosclerosis (FSGS). DDS patients typically present early-onset diffuse * Correspondence: [email protected] † Daisuke Matsuoka and Shunsuke Noda contributed equally to this work. 7 Second Department of Internal Medicine, Division of Nephrology, Kansai Medical University, 2-5-1 Shinmachi Hirakata, Osaka 573-1191, Japan Full list of author information is available at the end of the article
mesangial sclerosis (DMS), a 46,XY disorder of sex differentiation, and Wilms tumor (WT). FS patients tend to exhibit milder phenotypes with an onset at adolescence, including FSGS, male-to-female sex reversal, and gonadoblastoma, but usually lack WT [1]. Given the high incidence of WT and gonadoblastoma in DDS and FS, prophylactic gonadectomy and nephrectomies are recommended [1]. Over 95% of DDS patients carry missense mutations in exons 8 and 9, whereas FS is commonly caused by a splice-donor site
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