Co-localization of IgG with nephrin in immune-mediated idiopathic nephrotic syndrome.

Background: Increased serum anti-nephrin antibody titers and co-localization of nephrin and IgG in kidney tissues have been reported in minimal change disease (MCD) and post-transplant recurrent focal segmental glomerulosclerosis (FSGS). These results indicate an association of anti-nephrin antibodies with nephrotic syndrome (NS); however, the exact relationship remains unclear. Herein, we evaluated nephrin/IgG co-localization in the glomeruli of patients with various kidney diseases, including monogenic NS, to clarify the association between idiopathic nephrotic syndrome (INS) and anti-nephrin antibodies.

Prolonged hypokalemia long after causative factor elimination in pseudo-Bartter/Gitelman syndrome.

Background: Pseudo-Bartter/Gitelman syndrome (PBS/PGS) is caused by medication and lifestyle factors, leading to hypokalemia and potentially impairing kidney function. Treatment primarily involves eliminating the underlying causes, which typically results in rapid improvement. However, PBS/PGS findings may persist long after the removal of causative factors, and its pathogenesis remains unclear.

Clinical characteristics of patients with SALL1-related disorder.

Background: The Spalt-like transcription factor 1 (SALL1) gene is essential for kidney development. Pathogenic SALL1 variants cause Townes-Brocks syndrome 1 (TBS1), which typically presents with imperforate anus, dysplastic ears, and digital anomalies. However, clinical features vary widely.

Potential involvement of abnormal splicing in severe WT1-related disorders.

Introduction: WT1-related disorders are associated with WT1 gene variants. Recent advances in genetic medicine have led to a better understanding of the genotype-phenotype correlation in WT1-related diseases, particularly missense variants in exons 8 or 9 that lead to a wide range of severities. Exonic variants can lead to splicing abnormalities in rare diseases.

Comprehensive Splice Pattern Analysis for Previously Reported Splicing Variants and Their Phenotypic Contributions.

Introduction: Two distinct phenotypes of Dent disease-2 and Lowe syndrome are caused by () abnormality. Previous genetic studies demonstrated that truncating variants in exons 1 to 7 results in Dent disease-2 and in exons 8 to 24, result in Lowe syndrome. Recently, we successfully identified a functional isoform, whose altered initiation codons (Met187 and Met206) in exon 8 can affect the -truncating variant phenotypes.

Relationship between clinical and pathologic findings and the presence of genetic variants in patients with steroid-resistant nephrotic syndrome.

Background: Genetic analysis, crucial in determining treatment strategies for steroid-resistant nephrotic syndrome (SRNS), can be performed in limited facilities and requires a long time. Predicting the presence or absence of genetic variants by clinical and pathologic features is preferable.

Methods: In this multicenter, retrospective study, we compared the clinical or pathologic features between the patients with and without genetic variants in children with SRNS and evaluated the efficacy of immunosuppressive treatment and long-term kidney outcomes.

The first case of Al-Raqad syndrome in Japan is associated with a homozygous DCPS exonic variant resulting in aberrant splicing.

Background: Cases of unexplained neurodevelopmental disorder (NDD) are often accompanied by multiple congenital anomalies. With recent advances in genetic analysis technology, whole-exome sequencing (WES) has become a powerful diagnostic tool for unexplained NDD patients, but variants of unknown significance are sometimes detected in them.

Methods: WES identified a variant in a 2-year-old boy with NDD associated with multiple congenital anomalies who had no abnormal findings in G-banding and array comparative genomic hybridization (array CGH).

Clinical use of the VNtyper-Kestrel pipeline for MUC1 variant detection in autosomal-dominant tubulointerstitial kidney disease.

Background: Autosomal-dominant tubulointerstitial kidney disease caused by MUC1 (ADTKD-MUC1) is a rare disorder characterized by progressive kidney dysfunction. Pathogenic variants in MUC1 are difficult to detect owing to the variable number tandem repeat region. To address this issue, VNtyper-Kestrel, a bioinformatics pipeline for short-read sequencing data, was recently developed.

Differences in kidney prognosis between congenital and infantile nephrotic syndrome.

Background: More than half of patients with congenital nephrotic syndrome (CNS) or infantile nephrotic syndrome (infantile NS) have a monogenic aetiology. This study aimed to clarify differences in the clinical course, genetic background, and genotype-phenotype correlation between CNS and infantile NS.

Methods: We enrolled patients who were diagnosed with CNS or infantile NS and referred to our hospital for genetic analysis and investigated the clinical characteristics and genetic background of patients with identified causative genes.

Genetic aspects of pediatric nephrotic syndrome and anti-nephrin antibodies.

Nephrotic syndrome is the most common glomerular disease in children, and various hypotheses regarding its etiology have been proposed, primarily focusing on immune-related mechanisms. Nephrotic syndrome can manifest as a monogenic disease caused by deleterious variants in genes such as NPHS1, which encodes nephrin. In steroid-sensitive nephrotic syndrome, HLA class II and immune-related genes have been identified as susceptibility genes.

Intronic Variants at Third to Fifth Nucleotides Cause Alport Syndrome.

Introduction: Alport syndrome (AS) is an inherited kidney disease caused by variants in the , or genes, resulting in type IV collagen abnormalities. Although autosomal dominant variants in and are increasingly being diagnosed, X-linked AS (XLAS) caused by variants predominates. Single nucleotide substitutions in introns positioned at first and second from the last nucleotide (called a consensus sequence) of exons always cause aberrant splicing.

Phenotype and genotype of autosomal dominant tubulointerstitial kidney disease in a Japanese cohort.

Background: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is characterized by tubular atrophy, interstitial fibrosis, and progressive kidney dysfunction. Its causative genes include UMOD, MUC1, REN, HNF1B, and SEC61A1. ADTKD contributes to unexplained chronic kidney disease (CKD), and many cases remain genetically undiagnosed.

12-Year-old girl with systemic lupus erythematosus complicated by gangrene and intermittent claudication.

Systemic lupus erythematosus (SLE) can present with various symptoms, including rare manifestations such as gangrene. This report describes a 12-year-old girl with SLE who presented with intermittent claudication and gangrene. Although intermittent claudication is rare in paediatric cases, it is essential to consider vascular diseases including those associated with SLE as a potential cause.

Resurgence of Kawasaki Disease Following Relaxation of Coronavirus Disease 2019 Pandemic Restrictions in Japan.

Objective: To compare the number and incidence of Kawasaki disease (KD) patients in years 2 through 4 of the coronavirus disease 2019 pandemic, and determine the impact of 3 years of implementation of infection control measures and their subsequent relaxation on the epidemiology of KD in Japan.

Study Design: We conducted a population-based, cohort study including consecutive KD patients in Kobe City between 2021 and 2023. We compared the incidence of KD cases, in relation to timing of infection control measures, as well as infectious disease cases based on a regional surveillance system.

Clinical, Pathological, and Genetic Characteristics of Patients with Digenic Alport Syndrome.

Key Points: Patients with both and variants exhibited poor renal prognosis compared with those with autosomal dominant Alport syndrome. The proportion of patients with digenic Alport syndrome was 1.7% among all patients with Alport syndrome.

Genotype and X-chromosome inactivation are associated with disease severity in females with X-linked Alport syndrome.

Background: Male patients with X-linked Alport syndrome (XLAS) generally develop end-stage kidney disease in early or middle adulthood and show distinct genotype-phenotype correlations. However, female patients show various phenotypes ranging from asymptomatic to severe with no genotype-phenotype correlations. The factors affecting the severity of XLAS in female patients are unclear.

MYH9-related disease with a normal platelet count.

MYH9-related disease (MYH9-RD) is characterized by congenital macrothrombocytopenia, progressive kidney failure, and sensorineural hearing loss. We describe a patient with MYH9-RD and a normal platelet count. A 13-year-old boy with a normal platelet count presented with proteinuria and hematuria and underwent a kidney biopsy.

In steroid-resistant nephrotic syndrome that meets the strict definition, monogenic variants are less common than expected.

Background: In patients with steroid-resistant nephrotic syndrome (SRNS), the presence of monogenic variants influences therapeutic strategies. Large cohort studies reported the detection of monogenic variants in approximately 30% of patients with SRNS. However, these cohorts included many patients, such as those with symptomatic proteinuria, who did not meet the strict diagnostic criteria for pediatric nephrotic syndrome (NS).

Evaluation of pathogenicity of WT1 intron variants by in vitro splicing analysis.

Background: Wilms tumor 1 (WT1; NM_024426) causes Denys-Drash syndrome, Frasier syndrome, or isolated focal segmental glomerulosclerosis. Several WT1 intron variants are pathogenic; however, the pathogenicity of some variants remains undefined. Whether a candidate variant detected in a patient is pathogenic is very important for determining the therapeutic options for the patient.

Clinical characteristics and outcomes of immune-complex membranoproliferative glomerulonephritis and C3 glomerulopathy in Japanese children.

Background: Membranoproliferative glomerulonephritis (MPGN) can be divided into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G), which includes dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). These conditions result from abnormalities in different complement pathways and may lead to different prognoses. However, there are limited studies describing the respective clinical courses.