Infantile Nephrotic Syndrome Research Articles

Clinical and Genetic Differences between Congenital and Infantile Nephrotic Syndrome

Clinical and Genetic Differences between Congenital and Infantile Nephrotic Syndrome

Консервативная тактика ведения врожденного и инфантильного нефротического синдрома: опыт одного центра

Treatment tactics for patients with congenital nephrotic syndrome (CNS) varies from aggressive kinds, such as early nephrectomy, to conservative ones that include diuretic and nutritional support. The purpose of this research was to assess the effectiveness of conservative treatment of children with congenital and infantile nephrotic syndromes. Materials and methods used: a single-center retrospective study of 11 pediatric patients who had been manifested with NS within their first year of life and had required diuretic therapy, was conducted. The effectiveness of conservative therapy was assessed as preservation of the renal function according to glomerular filtration and satisfactory weight/height and height alone parameters’ dynamics that ensure the safety of kidney transplantation. Results: despite the molecular genetic study was conducted in all 250 children with NS, the described 11 have had verified pathogenic variants as follows: in the NPHS1 gene in 5 (45.5%, CI 16.8-76.6%), in the NPHS2 gene in another 5 (45.5%, CI 16.8-76.6%) and a single patient with none of a kind. It was revealed that despite the persistence of pronounced NS laboratory activity, the edema gradually disappeared against the background of conservative therapy, which in its turn had made it possible to refrain from early nephrectomy as well as to begin the renal replacement therapy over the age of 3 (4) y/o. 9 (81.8%, CI 48.2-97.7%) had satisfactory weight and height parameters at the age of 3 y/o. Only a single patient had undergone the early nephrectomy at the age of 4 months old, that was then followed by a successful kidney transplant at the age of 1 year and 4 months old, which, however, did not affect the then positive height prognosis. Conclusion: thus, reasonably selected conservative therapy for CNS can be effective against edematous syndrome and contribute to satisfactory weight/height growth parameters without early nephrectomy and, accordingly, the start of dialysis during the first year of life.

Clinical presentations and outcomes of congenital and infantile nephrotic syndrome.

Objective: To describe the characteristics and outcomes of congenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS). Study Design: Cross-sectional study. Setting: Department of Pediatric Nephrology, National Institute of Child Health, Karachi, Pakistan. Period: July 2023 to January 2024. Methods: All cases of CNS or INS visiting the outpatient, emergency department, or admitted in Nephrology ward were analyzed. Data including demographic characteristic and anthropometric measurements, clinical history and presentation were noted. Short-term outcomes in terms of cases who were discharged from hospital or those who died were recorded. Results: In a total of 33 infants, 17 (51.5%) were male. The mean age was 5.8±3.2 months. The mean days from onset of edema to the time of enrollment was 33.27±22.63 days. The most common presenting features were ascites noted in 4 (12.1%). Associated infections were reported in 21 (63.6%) infants. INS and CNS were noted in 25 (75.8%) and 8 (24.2%) infants respectively. Mortality was reported in 11 (33.3%) infants. Conclusion: Infections were the most common associated conditions in congenital and infantile nephrotic syndrome. Short term outcomes exhibiting high mortality rates warrants early identification and treatment of congenital and infantile nephrotic syndrome.

Multiple gene mutations in cytomegalovirus positive infantile nephrotic syndrome: a case report

Multiple gene mutations in cytomegalovirus positive infantile nephrotic syndrome: a case report

Genotype-Phenotype Associations in Patients with Congenital and Infantile Nephrotic Syndrome

Genotype-Phenotype Associations in Patients with Congenital and Infantile Nephrotic Syndrome

Congenital Nephrotic Syndrome: About A Case

Summary: Congenital nephrotic syndrome is a nephrotic syndrome present from birth or in the first three months of life, while infantile nephrotic syndrome is defined by a later onset but in the first year of life. Finnish-type congenital nephrotic syndrome and diffuse mesangial sclerosis represent the two main etiologies. Accurate diagnosis is based on clinical, histological and molecular biology criteria, and antenatal diagnosis is possible in some cases. We report the case of a female newborn, premature 35 WA + 9J, without particular pathological ATCDS admitted on D1 of life for a positive infectious assessment objectifying a bicytopenia made of thrombocytopenia and a neutropenia requested following an infectious anamnesis. positive in the mother, put on ATB, the evolution was marked by the appearance of edema of the two lower limbs on D6 of hospitalization taking the bucket in front generalized with puffiness of the face on D13 of hospitalization, a biological assessment was made and confirmed the nephrotic syndrome: hypoproteinemia at 20.3 g/l + hypoalbuminemia at 10.3 g/l + proteinuria for 24 hours at 3.3 g/24 hours proteinuria/creatinuria ratio 55. Associated symptomatic treatment nephroprotective treatment based on converting enzyme inhibitors was started with regular monitoring of renal function. In conclusion the congenital and infantile nephrotic syndromes are rare and generally have a poor prognosis whose evolution towards terminal renal insufficiency requires a program of dialysis and renal transplantationto the in the intensive Care Department A1 of the Hassan II University Hospital of Fez for the management of CT.

An 8-month-old boy with infantile nephrotic syndrome caused by semaphorin 3B-associated membranous nephropathy.

We present a case of nephrotic syndrome caused by semaphorin 3B-associated membranous nephropathy. The patient was an 8-month-old male infant who presented with severe proteinuria and hypertension. He was treated with prednisolone (PSL) for nephrotic syndrome; however, remission was not achieved within 4weeks. He was diagnosed with steroid-resistant nephrotic syndrome and underwent kidney biopsy. Pathological examination revealed membranous nephropathy with IgG deposits on both the glomerular basement membrane (GBM) and the tubular basement membrane (TBM). He was treated with cyclosporine (CsA) in addition to PSL and achieved complete remission. However, frequent relapses occurred after the discontinuation or tapering of immunosuppressants. Two years after treatment initiation, a second biopsy was performed and showed worsening of the disease, which required treatment with several immunosuppressants to achieve complete remission. After that, we performed additional immunostaining for semaphorin 3B, which confirmed the diagnosis of semaphorin 3B-associated membranous nephropathy. Although extremely rare in infantile cases, semaphorin 3B-associated membranous nephropathy should be considered in the differential diagnosis, as strong treatment with immunosuppressants might be needed. In addition, mycophenolate mofetil showed an effective clinical response in this case, indicating that it can be considered for future treatment strategies.

Features of congenital and infantile nephrotic syndrome in Russian children

Introduction. Nephrotic syndrome (NS) with an onset in the first year of life is one of the actual problems in pediatric nephrology due to the limited therapeutic options, the ineffectiveness of immunosuppressive therapy, and inevitable progression to chronic kidney disease (CKD). The basis of congenital NS (CNS) and infantile NS (INS) is a genetically determined pathology of podocytes. The timely verification of such pathology allows avoiding ineffective therapy and helps to predict outcomes. Aim. To determine CNS and INS’s clinical and molecular genetic characteristics in Russian children. Materials and methods. This study performed molecular genetic testing of 99 children with an early onset of NS. Results. In children with CNS and INS, the genetic cause of the disease was verified in 85%. Causative nucleotide variants prevailed in the NPHS1, NPHS2, WT1 genes. It became possible to identify the significant nucleotide variants for the Russian group of children. Children with NS at an early age turned out to be resistant to therapy with calcineurin inhibitors, which should be considered when choosing therapy tactics. Conclusion. We detected the genetic structure of congenital and infantile NS in the Russian Federation during the study. We analyzed the effectiveness of therapy with calcineurin inhibitors and the rate of CKD progression in this group.

High Incidence of COL4A Genetic Variants Among a Cohort of Children With Steroid-Resistant Nephrotic Syndrome From Eastern India

High Incidence of COL4A Genetic Variants Among a Cohort of Children With Steroid-Resistant Nephrotic Syndrome From Eastern India

Infantile nephrotic syndrome, immunodeficiency and adrenal insufficiency-a rare cause: Questions.

Infantile nephrotic syndrome, immunodeficiency and adrenal insufficiency-a rare cause: Questions.

Infantile nephrotic syndrome, immunodeficiency and adrenal insufficiency-a rare cause: Answers.

Infantile nephrotic syndrome, immunodeficiency and adrenal insufficiency-a rare cause: Answers.

Clear Evidence of LAMA5 Gene Biallelic Truncating Variants Causing Infantile Nephrotic Syndrome.

Pathogenic variants in single genes encoding podocyte-associated proteins have been implicated in about 30% of steroid-resistant nephrotic syndrome (SRNS) patients in children. However, LAMA5 gene biallelic variants have been identified in only seven patients so far, and most are missense variants of unknown significance. Furthermore, no functional analysis had been conducted for all but one of these variants. Here, we report three patients with LAMA5 gene biallelic truncating variants manifesting infantile nephrotic syndrome, and one patient with SRNS with biallelic LAMA5 missense variants. We conducted comprehensive gene screening of Japanese patients with severe proteinuria. With the use of targeted next-generation sequencing, 62 podocyte-related genes were screened in 407 unrelated patients with proteinuria. For the newly discovered LAMA5 variants, we conducted in vitro heterotrimer formation assays. Biallelic truncating variants in the LAMA5 gene (NM_005560) were detected in three patients from two families. All patients presented with proteinuria within 6 months of age. Patients 1 and 2 were siblings possessing a nonsense variant (c.9232C>T, p.[Arg3078*]) and a splice site variant (c.1282 + 1G>A) that led to exon 9 skipping and a frameshift. Patient 3 had a remarkable irregular contour of the glomerular basement membrane. She was subsequently found to have a nonsense variant (c.8185C>T, p.[Arg2720*]) and the same splice site variant in patients 1 and 2. By in vitro heterotrimer formation assays, both truncating variants produced smaller laminin α5 proteins that nevertheless formed trimers with laminin β1 and γ1 chains. Patient 4 showed SRNS at the age of 8 years, and carried compound heterozygous missense variants (c.1493C>T, p.[Ala498Val] and c.8399G>A, p.[Arg2800His]). Our patients showed clear evidence of biallelic LAMA5 truncating variants causing infantile nephrotic syndrome. We also discerned the clinical and pathologic characteristics observed in LAMA5-related nephropathy. LAMA5 variant screening should be performed in patients with congenital/infantile nephrotic syndrome.

Rare presentation of primary hepatic marginal zone B-cell lymphoma and membranous glomerulopathy in a 3-year-old boy

Abstract Introduction/Objective Primary hepatic marginal zone B-cell lymphoma (MZL) is a rare entity that has been described with chronic inflammatory disorders such as chronic viral hepatitides B and C and primary biliary cholangitis. We report MZL in a 3-year-old African-American boy that was discovered incidentally at autopsy. Methods/Case Report The patient first came to medical attention at 9-months of age with bilateral periorbital edema that progressed to generalized edema of the[PL1] face, extremities, and abdomen. Laboratory testing showed nephrotic syndrome with massive proteinuria (50-60 g/day). A percutaneous renal biopsy specimen showed membranous glomerulopathy with PLA2R detected by immunofluorescence, and granular IgG deposition along tubular basement membranes. Serum was negative for anti-PLA2R antibodies. The patient suffered recurrent upper respiratory tract infections requiring several intensive care hospitalizations. At 3 years of age, he was transported unresponsive and pulseless to the emergency department where he was pronounced dead. A brother with the infantile nephrotic syndrome had died from sepsis at 2 years of age. Suspicion of abuse led to an autopsy by the medical examiner, who discovered nodular masses in the right and left liver lobes, which histologically showed a serpiginous infiltrate of small B-lymphocytes positive for CD20, CD43 admixed with plasmacytoid cells with kappa light chain restriction. There were no extrahepatic tumors. Transmission electron microscopy of glomeruli showed membranous glomerulopathy. Kidneys showed dense reactive interstitial lymphocytic infiltrate with germinal centers Results (if a Case Study enter NA) NA Conclusion To our knowledge, this is the first reported case of MZL presenting in a pediatric patient with membranous glomerulopathy. Both diagnoses are associated with autoimmune diseases and persistent, chronic inflammation. Recurrent infections in this patient suggest an immunoregulatory disorder, setting the stage for chronic inflammation, as seen in the kidney, with progression to MZL in the liver.

Genotype-Phenotype Correlation in WT1 Exon 8 to 9 Missense Variants

IntroductionWT1 missense mutation in exon 8 or 9 causes infantile nephrotic syndrome with early progression to end-stage kidney disease (ESKD), Wilms tumor, and 46,XY female. However, some patients with missense mutations in exon 8 or 9 progress to ESKD in their teens or later. Therefore, we conducted a systematic review and functional analysis of WT1 transcriptional activity.MethodsWe conducted a systematic review of 174 cases with WT1 exon 8 or 9 missense variants from our cohort (n=13) and previous reports (n=161). Of these cases, mild and severe genotypes were selected for further in vitro functional analysis using luciferase assay.ResultsThe median age of developing ESKD was 1.17 years. A comparative study was conducted among three WT1 genotype classes: mutations of the DNA-binding site (DBS group), mutations outside the DNA-binding site but at sites important for zinc finger structure formation by 2 cysteines and 2 histidines (C2H2 group), and mutations leading to other amino acid changes (Others group). The DBS group showed the severest phenotype and the C2H2 group was intermediate, whereas the Others group showed the mildest phenotype (developing ESKD at 0.90, 2.00, and 3.92 years, respectively, with significant differences). In vitro functional analysis showed dominant-negative effects for all variants; in addition, the DBS and C2H2 mutations were associated with significantly lower WT1 transcriptional activity than the other mutations.ConclusionNot only the DNA-binding site but also C2H2 zinc finger structure sites are important for maintaining WT1 transcriptional activity, and their mutation causes severe clinical symptoms.

POS-130 EXPERIENCE WITH LEVAMISOLE IN CHILDREN WITH FREQUENTLY RELAPSING AND STEROID DEPENDENT NEPHROTIC SYNDROME HAVING FOLLOW UP AT TIKUR ANBESSA SPECIALIZED HOSPITAL, ADDIS ABABA, ETHIOPIA

Nephrotic syndrome is characterized by nephrotic range proteinuria, and hypoalbuminemia,most commonly associated with hyperlipidemia and edema. Without treatment,nephrotic syndrome in children is associated with high risk of death,most commonly from infections. Corticosteroids are the treatment of choice for idiopathic nephrotic syndrome (INS). Although about 80-90% of children with INS respond to corticosteroids, 20-30% become steroid dependent. Chronic corticosteroid therapy in patients with steroid dependent or frequently relapsing NS (FRNS or SDNS) is associated with numerous side effects. Levamisole is an anti helminthic agent with immunomodulatory effect. Levamisole has been considered the least toxic and least expensive steroid sparing drug for preventing relapses of steroid sensitive idiopathic nephrotic syndrome (SSINS). Though FDA doesn’t approve it for this purpose many researches done so far have shown that Levamisole is effective in treatment of children with FR/SDNS. We are using Levamisole in our Hospital but we have no data supporting or negating the use of levamisole as a good choice for treatment of children with SDNS/ FRNS to date. To determine the outcome of pediatric FR/SDNS treated with levamisole among children who had follow up at TASH pedaitric renal clinic. Methods: Retrospective cohort study on clinical records of patients with FR/SDNS having follow up at Tikur Anbessa Specialized Hospital from January 2016 to January 2019 . Charts of 80 patients reviewed and using exclusion criteria 33 patients were excluded from the study. Patient charts were retrieved using patients MRN and type of their disease from registration book at pediatrics renal clinic having follow up at our Hospital during the study period .The collected data was cleaned, Coded and analyzed using SPSS Version 25. Inclusion and Exclusion Criteria: Inclusion criteria: All patients who had FR/SD idiopathic nephrotic syndrome age between 1yr and 18 years attending follow up at TASH pediatric renal clinic. Exclusion criteria: All patients with steroid resistant nephrotic syndrome. All patients of Congenital or Infantile nephrotic syndrome. All patients with CKD. Nephrotic syndrome secondary to systemic illness Among 47 patients with FR/SDNS 32 were males and 15 were females, 21 (44.5%) were FRNS and 26 (55.5%) were SDNS. The duration of Nephrotic Syndrome was 8.75 3.7 yrs, the number of relapses before Levamisole treatment was 3, relapse after Levamisole was 0.7. The duration of Levamisole treatment was 19.9 during levamisole treatment. Levamisole is associated with significant reduction in relapses of FRNS/SDNS.It also significantly reduces adverse effects associated with corticosteroid treatment. The medication is not available in hospital pharmacies and treating those patients who have indications is difficult and the drug should be available at Hospital pharmacies.

Hereditary Congenital and Infantile Nephrotic Syndrome in Children: Strategy of Management with New Possibilities for Genetic Diagnosis and Therapy

Due to the worldwide genetic research, the fundamental information was obtained regarding the pathogenesis of the hormone-resistant congenital and infantile nephrotic syndrome in children. The mutations in the genes encoding the main components of the basement membrane of the kidney glomeruli, structural and functional podocyte proteins are responsible for the development of the congenital and infantile nephrotic syndrome with the typical histologic pattern of the diffuse mesangial sclerosis or focal segmental glomerulosclerosis. In accordance with the evidence-based international strategy, the clinical phenotyping combined with the targeted genetic analysis is the diagnosis standard for the hereditary nephrotic syndrome in children that are recommended to perform the genetic analysis prior to start of the steroid therapy and prior to the kidney biopsy. The early genetic diagnosis assures the personalized approach to the choice of the therapies considering the genotype and phenotype specifics of the congenital or infantile nephrotic syndrome in the particular child. The up-to-date strategy for the management of such children provides the carrying out of the conservative therapy and early transplantation of the related kidney when reaching 10-15 kg body weight (in this case, the kidneys are removed and transplanted during the same surgery), or the bilateral nephrectomy simultaneously or one stepped, then the second kidney and peritoneal dialysis, then kidney transplantation for the children reached 10-15 kg body weight. According to ESPN / ERA-EDTA register (2016), the 5-year survival rate of the children with the congenital nephrotic syndrome caused by NPHS1 gene mutation is 91% after kidney transplantation, 89% after allograft. The solutions for the pressing challenge of the domestic pediatrics are as the following: introduce the international strategy into the practice of the children management with the congenital and infantile nephrotic syndrome with the new possibilities of the genetic diagnosis and therapy replacing the kidney function; enhance the kidney transplantation and its availability; carry out the epidemiological studies of the hereditary nephrotic syndrome.

LAMA5 Gene Mutations in Japanese Cases with Infantile Nephrotic Syndrome

LAMA5 Gene Mutations in Japanese Cases with Infantile Nephrotic Syndrome

A cross-sectional nationwide survey of congenital and infantile nephrotic syndrome in Japan

BackgroundCongenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS) cause substantial morbidity and mortality. In Japan, there is a lack of knowledge regarding the characteristics of CNS and INS. This study aimed to clarify the characteristics of CNS and INS in Japan.MethodsThis cross-sectional nationwide survey obtained data from 44 institutions in Japan managing 92 patients with CNS or INS, by means of two survey questionnaires sent by postal mail. Patients aged < 16 years by 1 April 2015, with a diagnosis of CNS or INS, were included in this study. The primary outcome was end-stage kidney disease.ResultsA total of 83 patients with CNS or INS were analyzed. The most frequent disease type was non-Finnish (60.2%); 33 patients (39.8%) had Finnish type. Among those with non-Finnish-type disease, 26 had no syndrome and 24 had a syndrome, of which the most frequent was Denys–Drash syndrome (70.8%). Patients with non-Finnish-type disease with syndrome showed the earliest progression to end-stage kidney disease compared with the other two groups, whereas patients with non-Finnish-type disease without syndrome progressed more slowly compared with the other two groups. In the Finnish-type group, the disease was diagnosed the earliest; a large placenta was reported more frequently; genetic testing was more frequently performed (93.8%); mental retardation was the most frequent extra-renal symptom (21.2%); and thrombosis and infection were more frequent compared with the other groups. Patients with non-Finnish-type disease with syndrome had a higher frequency of positive extra-renal symptoms (79.2%), the most common being urogenital symptoms (54.2%). Treatment with steroids and immunosuppressants was more frequent among patients with non-Finnish-type disease without syndrome. Two patients with non-Finnish-type disease without syndrome achieved complete remission. In all groups, unilateral nephrectomy was performed more often than bilateral nephrectomy and peritoneal dialysis was the most common renal replacement therapy.ConclusionsThe present epidemiological survey sheds light on the characteristics of children with CNS and INS in Japan. A high proportion of patients underwent genetic examination, and patient management was in accord with current treatment recommendations and practices.Trial registrationNot applicable.

P1818CLINICAL AND MOLECULAR CHARACTERISTICS OF CHILDREN WITH WT-1-ASSOCIATED STEROID-RESISTANT NEPHROTIC SYNDROME

Abstract Background and Aims The Wilms tumor suppressor gene 1 (WT1) (MIM 607102) has an important role in renal and gonadal development. WT1 mutations was found to be associated with a large spectrum of phenotypes with autosomal-dominant inheritance, including Wilms tumor, Denys-Drash syndrome (DDS), Frasier syndrome (FS), and isolated steroid-resistant nephrotic syndrome (SRNS). The aim of the study was to investigate clinical and molecular characteristics in children with WT1-associated SRNS. Method Retrospective analysis of phenotype and genotype of six children (3M/3F) with SRNS and heterozygous WT1 mutations was performed. Karyotypes were available in all patients. Data on renal histology had three subjects with FS. The median follow-up period was 35.5 (IQR: 20.0; 57.5) months. WT1 mutations identified by direct Sanger sequencing (n=3) and next generation sequencing (n=3). Results The median age at onset of WT1-associated SRNS was 10.0 (IQR: 5.5; 22.5) months. 4/6 (66.7%) patients presented with infantile nephrotic syndrome and 2/6 (33.3%) with SRNS. Arterial hypertension was determined in 4/6 (66.7%) of individuals. Among children with WT1-associated SRNS 3/6 (50%) patients had DDS (2M/1F) and 3/6 (50%) subjects had FS (1M/2F). Children with DDS had Wilms tumor in 2/3 (66.7%) of cases and gonadal dysgenesis with hypospadias in 1/3 (33.3%) of children. Causative mutations were identified in all three patients with DDS, including 2 earlier described c.1384C&amp;gt;T in exon 9 and c.1098 + 1G&amp;gt;A in intron 6 in WT1 gene, and one novel mutation с.1378Т&amp;gt;G in exon 9. All DDS children had decreased eGFR to CKD stage 2-3 in two patients aged 7 and 11 years and ESKD in one child at the age of 2 years. All 3 patients with FS had focal segmental glomerulosclerosis on biopsy. Two phenotypic girls with FS had karyotype 46, XY and presented with pseudohermaphroditism. The same earlier described splice site mutation c.1432 + 5G&amp;gt;A in intron 9 in WT1 gene was identified in both cases. One boy with FS had typical male chromosome pattern (46, XY) and gonadal dysgenesis. Splice site mutation c.1432 + 4C&amp;gt;T in intron 9 in WT1 gene was found in the child. Nobody of patients with FS developed gonadoblastoma. Progression to CKD was found in all three cases with FS, including CKD stage 2-3 in two subjects aged 5 and 15 years and ESKD in one phenotypically girl with sex reversal developed at the age of 8 years. Conclusion We found that children with WT1-associated SRNS had a wide spectrum of renal and extrarenal phenotypes concerning the development of urogenital system and Wilms tumor with high risk of progression to CKD during childhood. Their phenotypes are clearly associated with the type and location of WT1 mutations led to DDS or FS. Genetic WT1 diagnostics is important in all children with SRNS for early detection, optimal treatment, tumor prevention and prognosis.

Comprehensive genetic diagnosis of Japanese patients with severe proteinuria

Numerous disease-causing gene mutations have been identified in proteinuric diseases, such as nephrotic syndrome and glomerulosclerosis. This report describes the results of comprehensive genetic diagnosis of Japanese patients with severe proteinuria. In addition, the report describes the clinical characteristics of patients with monogenic disease-causing mutations. We conducted comprehensive gene screening of patients who had either congenital nephrotic syndrome, infantile nephrotic syndrome, steroid-resistant nephrotic syndrome, or focal segmental glomerular sclerosis. Using targeted next-generation sequencing, 60 podocyte-related genes were screened in 230 unrelated patients with proteinuria. A retrospective review of clinical data was conducted for these patients. We detected monogenic disease-causing mutations in 30% (69 of 230) of patients among 19 of the screened genes. Common genes with disease-causing mutations were WT1 (25%), NPHS1 (12%), INF2 (12%), TRPC6 (10%), and LAMB2 (9%). With various immunosuppressive or renoprotective therapies, remission of proteinuria in patients with unknown causative mutations was observed in 26% of patients, whereas only 5% of patients with monogenic disease-causing mutations exhibited complete remission. We assessed the genetic backgrounds of Japanese patients with severe proteinuria. The proportion of patients with gene defects was similar to that of other reports, but the disease-causing gene mutation frequency was considerably different.