A5028322843- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- RNA modifications and cancer
- Amino Acid Enzymes and Metabolism
- Neonatal Health and Biochemistry
- Genomics and Rare Diseases
- Diet and metabolism studies
- Biochemical and Molecular Research
- Genetics and Neurodevelopmental Disorders
- Peroxisome Proliferator-Activated Receptors
- Lysosomal Storage Disorders Research
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Drug Transport and Resistance Mechanisms
- Folate and B Vitamins Research
- Coenzyme Q10 studies and effects
- RNA and protein synthesis mechanisms
- Metabolomics and Mass Spectrometry Studies
- Lipoproteins and Cardiovascular Health
- RNA Research and Splicing
- Blood disorders and treatments
- Neurological diseases and metabolism
- Diabetes and associated disorders
- RNA regulation and disease
- Heterotopic Ossification and Related Conditions
Saitama Medical University
2016-2025
Saitama Medical University Hospital
2016-2025
La Trobe University
2003-2024
Genomics Medicine (Ireland)
2023
Maebashi Institute of Technology
2020
Délégation Paris 7
2018
Institut Jacques Monod
2018
John Wiley & Sons (United States)
2018
Hudson Institute
2018
CARE Canada
2018
Mitochondrial disorders have the highest incidence among congenital metabolic characterized by biochemical respiratory chain complex deficiencies. It occurs at a rate of 1 in 5,000 births, and has phenotypic genetic heterogeneity. Mutations about 1,500 nuclear encoded mitochondrial proteins may cause dysfunction energy production disorders. More than 250 genes that been reported to date. However exact diagnosis for patients still remained largely unknown. To reveal this heterogeneity, we...
Abstract Background Lack of functional evidence hampers variant interpretation, leaving a large proportion individuals with suspected Mendelian disorder without genetic diagnosis after whole genome or exome sequencing (WES). Research studies advocate to further sequence transcriptomes directly and systematically probe gene expression defects. However, collection additional biopsies establishment lab workflows, analytical pipelines, defined concepts in clinical interpretation aberrant are...
Complex I of the respiratory chain is composed at least 45 subunits that assemble together mitochondrial inner membrane. Defects in human complex result energy generation disorders and are also implicated Parkinson's disease altered apoptotic signaling. The assembly this poorly understood complicated by its large size regulation two genomes, with seven encoded DNA (mtDNA) remainder nuclear genes. Here we analyzed a number mtDNA- nuclear-gene-encoded into I. We found mtDNA-encoded first...
Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by congenital malformation of the great toes and progressive heterotopic bone formation in muscle tissue. Recently, mutation involving single amino acid substitution morphogenetic protein (BMP) type I receptor, ALK2, was identified patients with FOP. We report here that identical mutation, R206H, observed 19 Japanese sporadic This mutant ALK2(R206H), activates BMP signaling without ligand binding....
Complex I deficiency, the most common respiratory chain defect, is genetically heterogeneous: mutations in 8 nuclear and 7 mitochondrial DNA genes encoding complex subunits have been described. However, these account for disease only a minority of I–deficient patients. We investigated whether there may be an unknown gene by performing functional complementation analysis cell lines from 10 unrelated Two patients were found to mutations. The other represented different (nuclear) groups, all...
Respiratory chain deficiencies exhibit a wide variety of clinical phenotypes resulting from defective mitochondrial energy production through oxidative phosphorylation. These defects can be caused by either mutations in the mtDNA or nuclear genes coding for proteins. The underlying pathomechanisms affect numerous pathways involved physiology. By whole-exome and candidate gene sequencing, we identified 11 individuals 9 families carrying compound heterozygous homozygous GTPBP3, encoding...
Although mitochondrial disorders are clinically heterogeneous, they frequently involve the central nervous system and among most common neurogenetic disorders. Identifying causal genes has benefited enormously from advances in high-throughput sequencing technologies; however, once defect is known, researchers face challenge of deciphering underlying disease mechanism. Here we characterize large biallelic deletions region encoding ATAD3C, ATAD3B ATAD3A genes. high homology complicates genomic...
Modified uridine containing taurine, 5-taurinomethyluridine (τm5U), is found at the anticodon first position of mitochondrial (mt-)transfer RNAs (tRNAs). Previously, we reported that τm5U absent in mt-tRNAs with pathogenic mutations associated diseases. However, biogenesis and physiological role remained elusive. Here, elucidated by confirming 5,10-methylene-tetrahydrofolate taurine are metabolic substrates for formation catalyzed MTO1 GTPBP3. GTPBP3-knockout cells exhibited respiratory...
Abstract Objective Short‐chain enoyl‐CoA hydratase ( ECHS 1) is a multifunctional mitochondrial matrix enzyme that involved in the oxidation of fatty acids and essential amino such as valine. Here, we describe broad phenotypic spectrum pathobiochemistry individuals with autosomal‐recessive 1 deficiency. Methods Using exome sequencing, identified ten unrelated carrying compound heterozygous or homozygous mutations . Functional investigations patient‐derived fibroblast cell lines included...
Primary coenzyme Q10 (CoQ10) deficiencies are rare, clinically heterogeneous disorders caused by mutations in several genes encoding proteins involved CoQ10 biosynthesis. is an essential component of the electron transport chain (ETC), where it shuttles electrons from complex I or II to III. By whole-exome sequencing, we identified five individuals carrying biallelic COQ4. The precise function human COQ4 not known, but seems play a structural role stabilizing multiheteromeric that contains...
Abstract Leigh syndrome (LS) is a progressive neurodegenerative disorder of infancy and early childhood. It clinically diagnosed by typical manifestations characteristic computed tomography (CT) or magnetic resonance imaging (MRI) studies. Unravelling mitochondrial respiratory chain (MRC) dysfunction behind LS essential for deeper understanding the disease, which may lead to development new therapies cure. The aim this study was evaluate clinical validity various diagnostic tools in...
This paper describes consensus statement by Joint Working Group Japan Pediatric Society and Atherosclerosis for Making Guidance of Familial Hypercholesterolemia (FH) in order to improve prognosis FH.FH is a common genetic disease caused mutations genes related low density lipoprotein (LDL) receptor pathway. Because patients with FH have high LDL cholesterol (LDL-C) levels from the birth, atherosclerosis begins develops during childhood which determines prognosis. Therefore, reduce their...
As atherosclerosis begins in childhood, early diagnosis and treatment of familial hypercholesterolemia (FH) is considered necessary. The basic pediatric FH (under 15 years age) based on hyper-low-density lipoprotein (LDL) cholesterolemia a family history FH; however, this guideline, to reduce overlooked cases, "probable FH" was established. Once diagnosed with or probable FH, efforts should be made promptly provide lifestyle guidance, including diet. It also important conduct an...
Both nuclear and mitochondrial DNA mutations can cause energy generation disorders. Respiratory chain complex I deficiency is the most common disorder a frequent of infantile encephalopathies such as Leigh's disease lethal disease. Most cases have been assumed to be caused by gene defects, but recently an increasing number shown in mitochondrially encoded subunit genes ND4, ND5, ND6. We report first four ND3 gene. Three unrelated children same novel heteroplasmic mutation (T10158C), only...
Abstract Context: Orthodenticle homeobox 2 (OTX2) is a transcription factor necessary for ocular and forebrain development. In humans, heterozygous mutations of OTX2 cause severe malformations. However, whether pituitary structural abnormalities or combined hormone deficiency (CPHD) has not been clarified. Objectives: We surveyed the functional consequences novel mutation that was detected in patient with anophthalmia CPHD. Patient: examined Japanese growth disturbance, anophthalamia,...
Complement component 1 Q subcomponent-binding protein (C1QBP; also known as p32) is a multi-compartmental whose precise function remains unknown. It an evolutionary conserved multifunctional localized primarily in the mitochondrial matrix and has roles inflammation infection processes, ribosome biogenesis, regulation of apoptosis nuclear transcription. N-terminal targeting peptide that proteolytically processed after import into matrix, where it forms homotrimeric complex organized...
Mutations in the m.13094T>C MT-ND5 gene have been previously described three cases of Leigh Syndrome (LS). In this retrospective, international cohort study we identified 20 clinically affected individuals (13 families) and four asymptomatic carriers. Ten patients were deceased at time analysis (median age death was 10 years (range: 5·4 months−37 years, IQR = 17·9 years). Nine manifested with LS, one mitochondrial encephalomyopathy, lactic acidosis stroke-like episodes (MELAS), Leber...
Originally, apomorphine was a broad-spectrum dopamine agonist with an affinity for all subtypes of the Dopamine D1 receptor to D5 receptor. We previously identified as potential therapeutic agent mitochondrial diseases by screening chemical library fibroblasts from patients diseases. In this study, we showed that prevented ferroptosis in various types well normal controls. Well-known biomarkers include protein markers such prostaglandin endoperoxide synthase 2 (PTGS2), key gene...
Abstract Respiratory chain complex I deficiency is a common cause of Leigh's disease (LD) and can be caused by mutations in genes encoded either nuclear or mitochondrial DNA (mtDNA). Most pathogenic mtDNA act recessively only when present at high mutant loads (typically >90%) tissues such as muscle brain. Two subunit genes, G14459A ND6 , T12706C ND5 have been associated with LD. We report another mutation, G13513A, three unrelated patients The G13513A mutation was approximately 50% less...