Heterozygous missense variant in TRPC6 in a boy with rapidly progressive infantile nephrotic syndrome associated with diffuse mesangial sclerosis

2021 ◽  
Author(s):  
Hiroaki Hanafusa ◽  
Yoshihiko Hidaka ◽  
Tomomi Yamaguchi ◽  
Hisashi Shimojo ◽  
Takanori Tsukahara ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Missense Variant ◽  
Diffuse Mesangial Sclerosis ◽  
Infantile Nephrotic Syndrome

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

2021 ◽  
Vol 65 (6) ◽  
pp. 12-21
Author(s):  
N. D. Savenkova
Keyword(s):  
Body Weight ◽  
Nephrotic Syndrome ◽  
Kidney Transplantation ◽  
Genetic Analysis ◽  
Genetic Research ◽  
Genetic Diagnosis ◽  
International Strategy ◽  
Diffuse Mesangial Sclerosis ◽  
Diagnosis And Therapy ◽  
Infantile Nephrotic Syndrome

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.

Nephrotic Mice (ICGN Strain): A Model of Diffuse Mesangial Sclerosis in Infantile Nephrotic Syndrome

1999 ◽  
Vol 19 (1) ◽  
pp. 73-82 ◽  
Author(s):  
Shinya Mizuno ◽  
Yoko Mizuno-Horikawa ◽  
Bing-Fei Yue ◽  
Munehiro Okamoto ◽  
Tsutomu Kurosawa
Keyword(s):  
Nephrotic Syndrome ◽  
Diffuse Mesangial Sclerosis ◽  
Infantile Nephrotic Syndrome

Genetics of congenital and infantile nephrotic syndrome

2019 ◽  
Vol 15 (2) ◽  
pp. 198-203 ◽  
Author(s):  
Sara Nawfal Sharief ◽  
Nada Abdullatif Hefni ◽  
Walaa Ali Alzahrani ◽  
Iman Ibrahim Nazer ◽  
Marwa Abdullah Bayazeed ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Infantile Nephrotic Syndrome

Infantile nephrotic syndrome and congenital glaucoma

2001 ◽  
Vol 16 (11) ◽  
pp. 894-897 ◽  
Author(s):  
J. A. Kari ◽  
Hussain Bamashmous ◽  
Sattam Lingawi ◽  
Essam Al-Sabban ◽  
Mohammed Akhtar
Keyword(s):  
Nephrotic Syndrome ◽  
Congenital Glaucoma ◽  
Infantile Nephrotic Syndrome

Congenital microcephaly and infantile nephrotic syndrome ? a case report

1994 ◽  
Vol 8 (1) ◽  
pp. 72-73 ◽  
Author(s):  
Fato? Yal�inkaya ◽  
Necmiye T�mer ◽  
Mesiha Ekim ◽  
Semanur Kuyucu ◽  
Nilg�n �akar ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Case Report ◽  
Infantile Nephrotic Syndrome ◽  
Congenital Microcephaly

scholarly journals Clear evidence of LAMA5 gene biallelic truncating variants causing infantile nephrotic syndrome

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0004952021
Author(s):  
Yukimasa Taniguchi ◽  
China Nagano ◽  
Kiyotoshi Sekiguchi ◽  
Atsushi Tashiro ◽  
Noriko Sugawara ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Splice Site ◽  
Japanese Patients ◽  
Compound Heterozygous ◽  
Missense Variants ◽  
Targeted Next Generation Sequencing ◽  
Pathogenic Variants ◽  
Infantile Nephrotic Syndrome ◽  
Splice Site Variant

Background: 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 7 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 SRNS case with biallelic LAMA5 missense variants. Methods: We conducted comprehensive gene screening of Japanese patients with severe proteinuria. Using 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. Results: Biallelic truncating variants in the LAMA5 gene (NM_005560) were detected in 3 patients from 2 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 eight and carried compound heterozygous missense variants (c.1493C>T, p.(Ala498Val) and c.8399G>A, p.(Arg2800His)). Conclusions: Our patients showed clear evidence of biallelic LAMA5 truncating variants causing infantile nephrotic syndrome. We also discerned the clinical and pathological characteristics observed in LAMA5-related nephropathy. LAMA5 variant screening should be performed in congenital/infantile nephrotic syndrome patients.

scholarly journals A Pattern of Glomerular Diseases in Egyptian Children: A Single-center Experience

2021 ◽  
Vol 9 (B) ◽  
pp. 1305-1312
Author(s):  
Hoda Atef Abdelsattar Ibrahim ◽  
Aya Amin ◽  
Ahmed Zeid ◽  
Samar Sabry ◽  
Hesham Safouh
Keyword(s):  
Nephrotic Syndrome ◽  
Iga Nephropathy ◽  
Glomerular Disease ◽  
Diffuse Mesangial Sclerosis ◽  
Gross Hematuria ◽  
Glomerular Diseases ◽  
Nephritic Syndrome ◽  
Study Results ◽  
Egyptian Children ◽  
Membranous Gn

BACKGROUND: Findings indicative of the glomerular disease are proteinuria, hematuria, nephrotic syndrome (NS), hypertension, and renal insufficiency. These presentations can be used to define different clinical patterns that resemble different underlying etiologies. METHODS: This study is a cross-sectional study enrolled in Children Hospital Cairo University. The study participants were recruited on two stages, retrospective and prospective stages. In the retrospective stage, all eligible patients across 5 years (between 2011 and 2015) with any glomerular disease were included in the study. In addition, prospectively, the new cases a long 6 months (from February 2016 till July 2016) with glomerular diseases were included in the study. RESULTS: A total of 594 cases with different glomerular diseases were identified. Cases were two groups: The retrospective group that involved 543 cases and the prospective group that included 51 cases. In the retrospective part of the study, the most common presentations were NS (68%), nephritis (16.4%), gross hematuria (10.5%), and nephrotic/nephritic syndrome (3.5%). The most common biopsies in the retrospective study were NS: MCNS (27.3%), NS: focal segmental glomerulosclerosis (FSGS) (23.4%), NS: Mesangioproliferative GN (9.4%), NS: Membranous GN (2.3%), Crescentric GN (3.9%), Membranous GN (0.8%), MPGN (0.8%), congenital nephrotic syndrome (CNS):Diffuse Mesangial Sclerosis (3.9%), CNS: Finnish type (2.3%), Alport (4.7%), IgA nephropathy (3.9%), IgM nephropathy (1.6%), lupus nephritis (LN) (3.1%), Thin basement membrane disease (3.1%), and others (9.4%) In the prospective study, the most common presentations were NS (76.5%), nephritis (11.8%), nephrotic/nephritic syndrome (7.8%), and gross hematuria (3.9%). The biopsies results were mainly NS: FSGS (33.3%) and NS: MCNS (33.3%). Other biopsies results in the prospective part were NS: Mesangioproliferative GN (16.7%), LN (8.3%), and IgA nephropathy (8.3%). CONCLUSION: The most common glomerular disease in childhood is NS. The most common pathology of glomerular diseases is minimal change NS.

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