A5024916957- Cell Adhesion Molecules Research
- Renal and related cancers
- Renal Diseases and Glomerulopathies
- Platelet Disorders and Treatments
- RNA Research and Splicing
- Biomedical Research and Pathophysiology
- Genetic and Kidney Cyst Diseases
- Genetic Syndromes and Imprinting
- RNA and protein synthesis mechanisms
- Lysosomal Storage Disorders Research
- RNA modifications and cancer
- Ion Transport and Channel Regulation
- Chronic Kidney Disease and Diabetes
- Genetics and Neurodevelopmental Disorders
- Cellular transport and secretion
- Polyamine Metabolism and Applications
- RNA regulation and disease
- Receptor Mechanisms and Signaling
- Connective tissue disorders research
- Metabolism and Genetic Disorders
- Vasculitis and related conditions
- Celiac Disease Research and Management
- Pancreatic function and diabetes
- Urticaria and Related Conditions
- Hormonal Regulation and Hypertension
Kobe University
2019-2024
Himeji Medical Center
2023-2024
Nagoya University
2020
Kobe Institute Of Computing
2020
Early kidney failure in the hereditary type IV collagen disease, Alport syndrome, can be delayed by renin-angiotensin inhibitors. However, whether all patients and different genotypes respond equally well to this kidney-protective therapy remains unclear. Here, we performed a retrospective study on 430 with male X-linked syndrome examine relationships among prognosis, genotype, treatment effect large cohort of Japanese patients. We analyzed clinical features, genotype-phenotype correlation,...
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 Japanese patients with severe proteinuria. In addition, clinical characteristics monogenic mutations. We conducted screening who had either congenital syndrome, infantile steroid-resistant or focal segmental glomerular sclerosis. Using targeted next-generation sequencing, 60...
Abstract Currently, there are no treatments for Alport syndrome, which is the second most commonly inherited kidney disease. Here we report development of an exon-skipping therapy using antisense-oligonucleotide (ASO) severe male X-linked syndrome (XLAS). We targeted truncating variants in exon 21 COL4A5 gene and conducted a type IV collagen α3/α4/α5 chain triple helix formation assay, vitro vivo treatment efficacy evaluation. show that skipping enabled trimer formation, leading to...
Abstract Gitelman syndrome is an autosomal recessive inherited salt-losing tubulopathy. It has a prevalence of around 1 in 40,000 people, and heterozygous carriers are estimated at approximately 1%, although the exact unknown. We predicted based on multiple genome databases, HGVD jMorp for Japanese population gnomAD other ethnicities, included all 274 pathogenic missense or nonsense variants registered HGMD Professional. The frequencies these alleles were summed to calculate total variant...
Autosomal dominant tubulointerstitial kidney disease (ADTKD)-MUC1 is predominantly caused by frameshift mutations owing to a single-base insertion into the variable number tandem repeat (VNTR) region in MUC1. Because of complexity variant hotspot, identification using short-read sequencers (SRSs) challenging. Although recent studies have revealed usefulness long-read (LRSs), prevalence MUC1 variants patients with clinically suspected ADTKD remains unknown. We aimed clarify this and genetic...
Abstract Background Alport syndrome (AS) is a hereditary disease caused by mutations in COL4A3‐5 genes. Recently, comprehensive genetic analysis has become the first‐line diagnostic tool for AS. However, no reports comparing mutation identification rates between conventional sequencing and screening have been published. Methods In this study, 441 patients clinically suspected of having AS were divided into two groups compared. The initial mutational method involved targeted exome using...
Frasier syndrome (FS) is a rare inherited kidney disease caused by intron 9 splicing variants of WT1. For wild-type WT1, 2 active splice donor sites in cause mixture essential transcripts (with or without lysine-threonine-serine [+/KTS -KTS]), and imbalance the +KTS/-KTS ratio results development FS. To date, 6 causative have been identified; however, detailed transcript analysis has not yet conducted genotype-phenotype correlation also remains to be elucidated.We an vitro minigene assay for...
COL4A5 is a causative gene of X-linked Alport syndrome (XLAS). Male patients with XLAS nonsense variants have the most severe phenotypes early onset end-stage kidney disease (ESKD); those splicing middle and missense mildest phenotypes. Therefore, genotyping for male can be used to predict prognosis. Single-base substitutions at last nucleotide position in each exon are known affect patterns could variants. Nevertheless, XLAS, these generally considered variants, without conducting...
WT1 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 mutations progress ESKD their teens later. Therefore, we conducted a systematic review functional analysis of transcriptional activity.We 174 cases variants from our cohort (n=13) previous reports (n=161). Of these cases, mild severe genotypes were selected for further vitro using luciferase assay.The median...
Abstract Background Fabry disease is an X-linked lysosomal storage disorder caused by insufficient α-galactosidase A (GLA) activity resulting from variants in the GLA gene, which leads to glycosphingolipid accumulation and life-threatening, multi-organ complications. Approximately 50 have been reported that cause splicing abnormalities . Most were found within canonical splice sites, are highly conserved GT AG acceptor donor dinucleotides, whereas one-third located outside making it...
Abstract X-linked Alport syndrome (XLAS) is a congenital renal disease caused by mutations in COL4A5 . In XLAS cases suspected of being aberrant splicing, transcript analysis needs to be conducted determine splicing patterns and assess the pathogenicity. However, such not always available. We functional assay using hybrid minigene for seven intronic mutations: one was identified us six were found Human Gene Mutation Database. The revealed exon skipping four variants, 10-bp insertion variant,...
Abstract Background X‐linked Alport syndrome (XLAS) is a progressive, hereditary glomerular nephritis of variable severity caused by pathogenic COL4A5 variants. Currently, genetic testing widely used for diagnosing XLAS; however, determining the pathogenicity variants detected such analyses can be difficult. Intronic or synonymous may cause inherited diseases inducing aberrant splicing. Transcript analysis necessary to confirm variants, but it sometimes difficult extract mRNA directly from...
Key Points LAMA5 gene biallelic variants have been identified in only seven patients so far, and no functional analysis had conducted for all but one. We report three with truncating manifesting infantile nephrotic syndrome vitro heterotrimer assays. one patient SRNS missense variants. Background Pathogenic single genes encoding podocyte-associated proteins implicated about 30% of steroid-resistant (SRNS) children. However, most are unknown significance. Furthermore, these Here, we syndrome,...
Key Points We investigated the association between focal segmental glomerulosclerosis histologic variants (Columbia classification) and monogenic variant detection rates. The perihilar had strongest with of variants. tip weakest Background Approximately 30% children steroid-resistant nephrotic syndrome (SRNS) have causative SRNS represents glomerular disease resulting from various etiologies, which lead to similar patterns damage. Patients mainly exhibit (FSGS). There is limited information...
Abstract Background In recent years, the elucidation of splicing abnormalities as a cause hereditary diseases has progressed. However, there are no comprehensive reports suspected variants in CLCN5 gene Dent disease cases. We reproduced mutations by mutagenesis, inserted mutated genes into minigene vectors, and investigated pathogenicity onset mechanisms these variants. Methods conducted functional assays using hybrid for six (c.105G>A, c.105+5G>C, c.106−17T>G, c.393+4A>G,...
Abstract Galactose-deficient IgA1 (Gd-IgA1) is important in the pathogenesis of IgA nephropathy (IgAN). A Gd-IgA1-specific monoclonal antibody (KM55) has revealed glomerular Gd-IgA1 deposition solely patients with IgAN and vasculitis nephritis (IgAV-N). However, this specificity controversial not been demonstrated pediatric patients. Here, we conducted double-immunofluorescence staining 60 various diseases. We divided into four groups: (1) IgAV-N (n = 23); (2) immunocomplex-mediated...
Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in the PKHD1 gene. The clinical spectrum often more variable than previously considered. We aimed to analyze features of genetically diagnosed ARPKD Japanese population.We conducted a genetic analysis patients with clinically or suspected Japan. Moreover, we performed minigene assay elucidate mechanisms that could affect phenotypes.PKHD1 pathogenic variants were identified 32 (0-46 years). Approximately one-third...
Although Lowe syndrome and Dent disease-2 are caused by Oculocerebrorenal of (OCRL) mutations, their clinical severities differ substantially molecular mechanisms remain unclear. Truncating mutations in OCRL exons 1-7 lead to disease-2, whereas those 8-24 syndrome. Herein we identified the mechanism underlying action novel protein isoforms.Messenger RNA samples extracted from cultured urine-derived cells a healthy control patient were examined detect 5' end isoform. For expression functional...
Abstract Gitelman syndrome (GS) is a rare, autosomal recessive, salt‐losing tubulopathy caused by loss of function in the SLC12A3 gene (NM_000339.2), which encodes natrium chloride cotransporter. The detection homozygous or compound heterozygous variants expected GS, but 18%–40% patients with clinical GS carry only one mutant allele. Previous reports identified some pathogenic deep intronic . Here, we report screening 13 suspected carrying mutated Variant used HaloPlex Target Enrichment...