In Vivo Expression of NUP93 and Its Alteration by NUP93 Mutations Causing Focal Segmental Glomerulosclerosis

Hashimoto, Taeko; Harita, Yutaka; Takizawa, Keiichi; Urae, Seiya; Ishizuka, Kiyonobu; Miura, Kenichiro; Horita, Shigeru; Ogino, Daisuke; Tamiya, Gen; Ishida, Hideyuki; Mitsui, Tetsuo; Hayasaka, Kiyoshi; Hattori, Motoshi

doi:10.1016/j.ekir.2019.05.1157

Cited by 14 publications

(23 citation statements)

References 39 publications

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“…[ 7 ] In addition, a case of SRNS caused by NUP93 a gene mutation was recently reported by Japanese scholars. [ 23 ] A case of SRNS caused by a novel compound heterozygous mutation of NUP93 , which has not been previously reported, is described herein.…”

Section: Introductionmentioning

confidence: 96%

Steroid-resistant nephrotic syndrome in infants caused by a novel compound heterozygous mutation of the NUP93

et al. 2021

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Rationale: Steroid-resistant nephrotic syndrome (SRNS) is a special kidney disease. SRNS is characterized by steroid-resistant, clinical variability, and genetic heterogeneity. Patients with SRNS often may eventually need renal transplantation. Patient concerns: A 10-month-old Chinese male infant presented with oliguria, renal dysfunction, hypertension, and anemia. Diagnoses: Combined with clinical manifestations, laboratory testing and sequencing results, the patient was diagnosed as SRNS. Interventions: Combined intravenous methylprednisolone and cefoperazone sulbactam did not improve the patient's condition. Thus, SRNS associated with hereditary nephrotic syndrome was strongly suspected. Genetic testing for hereditary renal disease of the patient revealed 2 novel heterozygous mutations in the Nucleoporin 93 ( NUP93 ) gene, which were predicted pathogenic and harmful by bioinformatic softwares of SIFT, PolyPhen_2 and REVEL. Outcomes: As general physical health deterioration and renal dysfunction, the patient died of a severe infection. Lessons: The novel NUP93 heterozygous mutations identified in the current study broadened the genetic spectrum of SRNS and further deepened our insight into pathogenic mutations of NUP93 to improve disease diagnosis.

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Section: Introductionmentioning

confidence: 96%

Steroid-resistant nephrotic syndrome in infants caused by a novel compound heterozygous mutation of the NUP93

et al. 2021

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“…Pathogenic mutations identified in patients with genetic FSGS (patient numbers 1–8) are shown in Supplementary Table 1 . The affected genes were NUP107 in three patients 10 , WT1 in two patients, and LAMB2 , INF2 , and NUP93 11 in one patient each. No patients with primary FSGS had pathogenic mutations in the 64 genes analyzed in the present study.…”

Section: Resultsmentioning

confidence: 98%

“…Patients with NPHS1 mutations were excluded because the disease onset was in infancy in all patients. Our study included three patients who were described in the previous reports 10 , 11 and five patients who were not described previously. The degree of FPE in a total of 46 patients from the literature and the present study is summarized in Table 2 .…”

Section: Resultsmentioning

confidence: 99%

Degree of foot process effacement in patients with genetic focal segmental glomerulosclerosis: a single-center analysis and review of the literature

Ishizuka

Miura

Hashimoto

et al. 2021

Sci Rep

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Determining the cause of focal segmental glomerulosclerosis (FSGS) has crucial implications for evaluating the risk of posttransplant recurrence. The degree of foot process effacement (FPE) on electron micrographs (EM) of native kidney biopsies can reportedly differentiate primary FSGS from secondary FSGS. However, no systematic evaluation of FPE in genetic FSGS has been performed. In this study, percentage of FPE and foot process width (FPW) in native kidney biopsies were analyzed in eight genetic FSGS patients and nine primary FSGS patients. All genetic FSGS patients showed segmental FPE up to 38% and FPW below 2000 nm, while all primary FSGS patients showed diffuse FPE above 88% and FPW above 3000 nm. We reviewed the literature which described the degree of FPE in genetic FSGS patients and identified 38 patients with a description of the degree of FPE. The degree of FPE in patients with mutations in the genes encoding proteins associated with slit diaphragm and cytoskeletal proteins was varied, while almost all patients with mutations in other FSGS genes showed segmental FPE. In conclusion, the present study suggests that the degree of FPE in native kidney biopsies may be useful for differentiating some genetic FSGS patients from primary FSGS patients.

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“…Nine patients with familial or syndromic FSGS and 28 patients who did not undergo genetic testing were also excluded. In the remaining 22 patients, whole exome sequencing with a focus on 53 genes associated with FSGS or targeted next-generation sequencing for 60 genes associated with FSGS were performed as previously reported (Supplementary Tables 1 and 2) [28,29]. Pathogenic mutations in FSGS genes were identi ed in seven patients, who were thus excluded from the study.…”

Section: Study Populationmentioning

confidence: 99%

Response to Steroid and Immunosuppressive Therapies May Predict Post-transplant Recurrence of Focal Segmental Glomerulosclerosis

Miura¹,

Ando²,

Kanda³

et al. 2021

Preprint

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Recurrence of focal segmental glomerulosclerosis (FSGS) is a major challenge in kidney transplantation. Several clinical factors, including initial steroid sensitivity, have been associated with increased post-transplant FSGS recurrence risk. However, conflicting data have been reported, possibly due to the heterogeneous pathophysiology of FSGS and the lack of genetic testing of FSGS patients. Further, the response to immunosuppressive therapies have not been evaluated. This study aimed to assess the risk factors for post-transplant recurrence in stringently selected patients based on a comprehensive clinicopathological evaluation and genetic testing. Fifty-nine patients aged 1–25 years at FSGS onset who underwent kidney transplantation between 2002 and 2018 were enrolled. Patients with secondary, familial, syndromic, and genetic FSGS and those who did not undergo genetic testing were excluded. Data from 15 kidney transplant recipients were analyzed. Nine (60%) patients experienced post-transplant FSGS recurrence, while six patients did not. The proportion of patients who achieved complete or partial remission with initial steroid and/or additional therapies with immunosuppressive agents and/or plasmapheresis was significantly higher in the FSGS recurrence group than the group without FSGS recurrence (P=0.04). In conclusion, this study suggests that the response to steroid treatment, other immunosuppressive agents, and/or plasmapheresis may predict post-transplant FSGS recurrence.

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In Vivo Expression of NUP93 and Its Alteration by NUP93 Mutations Causing Focal Segmental Glomerulosclerosis

Cited by 14 publications

References 39 publications

Steroid-resistant nephrotic syndrome in infants caused by a novel compound heterozygous mutation of the NUP93

Steroid-resistant nephrotic syndrome in infants caused by a novel compound heterozygous mutation of the NUP93

Degree of foot process effacement in patients with genetic focal segmental glomerulosclerosis: a single-center analysis and review of the literature

Response to Steroid and Immunosuppressive Therapies May Predict Post-transplant Recurrence of Focal Segmental Glomerulosclerosis

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