Naomi Tsuchida
A5077416181- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Otitis Media and Relapsing Polychondritis
- Genomic variations and chromosomal abnormalities
- Vascular Anomalies and Treatments
- Genetic Neurodegenerative Diseases
- Rheumatoid Arthritis Research and Therapies
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA regulation and disease
- Fetal and Pediatric Neurological Disorders
- Congenital heart defects research
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Congenital Ear and Nasal Anomalies
- Systemic Lupus Erythematosus Research
- Cellular transport and secretion
- Inflammatory Myopathies and Dermatomyositis
- Immunodeficiency and Autoimmune Disorders
- Ubiquitin and proteasome pathways
- Connective tissue disorders research
- IgG4-Related and Inflammatory Diseases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
Yokohama City University Hospital
2020-2025
Yokohama City University
2016-2025
Genomics (United Kingdom)
2023
Hakodate National Hospital
2020
Hudson Institute
2018
Université Paris Cité
2018
Délégation Paris 7
2018
Institut Jacques Monod
2018
Merck Institute for Science Education
2018
John Wiley & Sons (United States)
2018
To determine clinical and genetic features of individuals with relapsing polychondritis (RP) likely caused by pathogenic somatic variants in ubiquitin-like modifier activating enzyme 1 (UBA1).Fourteen patients RP who met the Damiani Levine criteria were recruited (12 men, 2 women; median onset age (IQR) 72.1 years (67.1-78.0)). Sanger sequencing UBA1 was performed using genomic DNA from peripheral blood leukocytes or bone marrow tissue. Droplet digital PCR (ddPCR) peptide nucleic acid...
We developed a diagnostic method for repeat expansion diseases using long-read sequencer to improve currently available, low throughput methods. employed the real-time target enrichment system of nanopore GridION adaptive sampling option, in which software-based assignment is available without prior sample enrichment, and built an analysis pipeline that prioritized disease-causing loci. Twenty-two patients with various neurological neuromuscular diseases, including 12 genetically diagnosed...
Interstitial lung disease (ILD) is the principal cause of death in polymyositis/dermatomyositis (PM/DM). Here we investigated prognostic factors for and serious infection PM/DM-ILD using multicenter database. We retrospectively reviewed baseline demographic, clinical laboratory findings, treatment regimens outcomes patients with PM/DM-ILD. The distribution ILD lesions was evaluated four divided zones high-resolution computed tomography images. Of 116 PM/DM-ILD, 14 died within 6 months from...
Abstract Although there are many known Mendelian genes linked to epileptic or developmental and encephalopathy (EE/DEE), its genetic architecture is not fully explained. Here, we address this incompleteness by analyzing exomes of 743 EE/DEE cases 2366 controls. We observe that damaging ultra-rare variants (dURVs) unique an individual significantly overrepresented in EE/DEE, both the other non-EE/DEE genes. Importantly, enrichment dURVs significant, even subset with diagnostic ( P =...
Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an autoinflammatory disease caused by variants in the UBA1 gene that lead to severe systemic inflammation and myelodysplastic syndrome. Although no standard therapy has been established yet, azacitidine bone marrow transplantation have reported be promising possibilities; however, indications for these treatments are problematic not necessarily applicable all patients. We previously results of short-term treatment...
Abstract Background Previous large-scale studies of de novo variants identified a number genes associated with neurodevelopmental disorders (NDDs); however, it was also predicted that many NDD-associated await discovery. Such can be discovered by integrating copy (CNVs), which have not been fully considered in previous studies, and increasing the sample size. Methods We first constructed model estimating rates CNVs per gene from several factors such as length exons. Second, we compiled...
Haploinsufficiency of A20 (HA20) is caused by loss-of-function TNFAIP3 variants. Phenotypic and genetic features HA20 remain uncertain; therefore, the clinical distinction between Behçet's disease (BD) requires clarification.We have collected 12 Japanese BD-like families. Probands these families were analyzed whole exome sequencing (WES) subsequent Sanger sequencing. Clinical compared 54 patients (including previously reported new cases) 520 BD patients.We identified c.1434C>A:p.(Cys478*) in...
Abstract A pentanucleotide TTTCA repeat insertion into a polymorphic TTTTA element in SAMD12 causes benign adult familial myoclonic epilepsy. Although the precise determination of entire sequence is important for molecular diagnosis and research, obtaining this remains challenging when using conventional genomic/genetic methods, even short-read long-read next-generation sequencing technologies have been insufficient. Incomplete information regarding expanded sequences may hamper our...
Tandem repeats (TRs) are one of the largest sources polymorphism, and their length is associated with gene regulation. Although previous studies reported several tandem regulating splicing in cis (spl-TRs), no large-scale study has been conducted. In this study, we established a genome-wide catalog 9537 spl-TRs total 58,290 significant TR-splicing associations across 49 tissues (false discovery rate 5%) by using Genotype-Tissue expression (GTex) Project data. Regression models explaining...
Abstract Objectives To efficiently detect somatic UBA1 variants and establish a clinical scoring system predicting patients with pathogenic in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Methods Eighty-nine Japanese clinically suspected syndrome were recruited [81 males 8 females; median age of onset 69.3 years (interquartile range 62.1–77.6)]. Peptide nucleic acid–clamping PCR (PNA-PCR), regular targeting exon 3 clustering subsequent Sanger sequencing...
Calcineurin is a calcium (Ca2+)/calmodulin-regulated protein phosphatase that mediates Ca2+-dependent signal transduction. Here, we report six heterozygous mutations in gene encoding the alpha isoform of calcineurin catalytic subunit (PPP3CA). Notably, were observed different functional domains: addition to three domain mutations, two missense found auto-inhibitory (AI) domain. One additional frameshift insertion caused premature termination was also identified. Detailed clinical evaluation...
Epilepsies are common neurological disorders and genetic factors contribute to their pathogenesis. Copy number variations (CNVs) increasingly recognized as an important etiology of many human diseases including epilepsy. Whole‐exome sequencing (WES) is becoming a standard tool for detecting pathogenic mutations has recently been applied CNVs. Here, we analyzed 294 families with epilepsy using WES, focused on 168 no causative single nucleotide variants in known epilepsy‐associated genes...
Abstract Background GGC repeat expansions in NOTCH2NLC are associated with neuronal intranuclear inclusion disease. Very recently, asymptomatic carriers were reported. In these individuals, the CpG island is hypermethylated, suggesting that two factors length and DNA methylation status should be considered to evaluate pathogenicity. Long-read sequencing can used simultaneously profile genomic epigenomic alterations. We analyzed four sporadic cases expansion their phenotypically normal...
PurposeThis study aimed to undertake a multidisciplinary characterization of the phenotype associated with SOX11 variants.MethodsIndividuals protein altering variants in were identified through exome and genome sequencing international data sharing. Deep clinical phenotyping was undertaken by referring clinicians. Blood DNA methylation assessed using Infinium MethylationEPIC array. The expression pattern developing human brain defined RNAscope.ResultsWe reported 38 new patients variants....
We discovered biallelic intragenic structural variations (SVs) in FGF12 by applying long-read whole genome sequencing to an exome-negative patient with developmental and epileptic encephalopathy (DEE). also found another DEE carrying a (homozygous) single-nucleotide variant (SNV) that was detected exome sequencing. heterozygous recurrent missense variants gain-of-function or entire duplication of are known causes epilepsy, but SNVs/SVs have never been described. encodes intracellular...
In various neurodevelopmental disorders (NDDs), sets of differential methylation marks (referred to as DNA signatures or episignatures) are syndrome-specific and useful in evaluating the pathogenicity detected genetic variants. These have generally been tested using arrays, requiring additional experimental evaluation costs. As an alternative, long-read sequencing can simultaneously accurately evaluate epigenetic changes. addition, genome-wide profiling with more complete CpG (than arrays)...
We report heterozygous CELF2 (NM_006561.3) variants in five unrelated individuals: Individuals 1-4 exhibited developmental and epileptic encephalopathy (DEE) Individual 5 had intellectual disability autistic features. encodes a nucleocytoplasmic shuttling RNA-binding protein that has multiple roles RNA processing is involved the embryonic development of central nervous system heart. Whole-exome sequencing identified following variants: two missense [c.1558C>T:p.(Pro520Ser) 1 2,...