The c.1617del variant of TMEM260 is identified as the most frequent single gene determinant for Japanese patients with a specific type of congenital heart disease.

Although the molecular mechanisms underlying congenital heart disease (CHD) remain poorly understood, recent advances in genetic analysis have facilitated the exploration of causative genes for CHD. We reported that the pathogenic variant c.1617del of TMEM260, which encodes a transmembrane protein, is highly associated with CHD, specifically persistent truncus arteriosus (PTA), the most severe cardiac outflow tract (OFT) defect.

Functional characterization of variants found in Japanese patients with hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant form of vascular dysplasia. Genetic diagnosis is made by identifying loss-of-function variants in genes, such as ENG and ACVRL1. However, the causal mechanisms of various variants of unknown significance remains unclear.

Difference in Clinical Phenotype, Mutation Position, and Structural Change of RNF213 Rare Variants Between Pediatric and Adult Japanese Patients with Moyamoya Disease.

It is unclear how rare RNF213 variants, other than the p.R4810K founder variant, affect the clinical phenotype or the function of RNF213 in moyamoya disease (MMD). This study included 151 Japanese patients with MMD.

Variant spectrum of PIEZO1 and KCNN4 in Japanese patients with dehydrated hereditary stomatocytosis.

Hereditary stomatocytosis (HSt) is a type of congenital hemolytic anemia caused by abnormally increased cation permeability of erythrocyte membranes. Dehydrated HSt (DHSt) is the most common subtype of HSt and is diagnosed based on clinical and laboratory findings related to erythrocytes. PIEZO1 and KCNN4 have been recognized as causative genes, and many related variants have been reported.

Loss-of-function mutations in SGCE found in Japanese patients with myoclonus-dystonia.

SGCE myoclonus-dystonia is a monogenic form of dystonia with an autosomal dominant mode of inheritance that co-occurs with a myoclonic jerk. In this study, we present 12 Japanese patients from nine families with this disease. Targeted next-generation sequencing covering major causative genes for monogenic dystonias identified nine distinct SGCE mutations from each of the families: three nonsense, two frameshift, two missense, one in-frame 15 bp deletion, and one splice donor site mutations, of which four were previously unreported.

Dystonic Tremor in Adult-onset DYT-KMT2B.

KMT2B-related dystonia (DYT28, DYT-KMT2B) is an inherited dystonia that generally begins in the lower limbs during childhood and evolves into generalized dystonia. We herein report a case of adult-onset DYT28 with dystonic tremor. A 27-year-old woman initially displayed right upper limb and cervical tremors over the course of 1 year.

Case Report: Long-Term Suppression of Paroxysmal Kinesigenic Dyskinesia After Bilateral Thalamotomy.

Paroxysmal kinesigenic dyskinesia (PKD) is a movement disorder characterized by transient dyskinetic movements, including dystonia, chorea, or both, triggered by sudden voluntary movements. Carbamazepine and other antiepileptic drugs (AEDs) are widely used in the treatment of PKD, and they provide complete remission in 80-90% of medically treated patients. However, the adverse effects of AEDs include drowsiness and dizziness, which interfere with patients' daily lives.

Replenishing exosomes from older bone marrow stromal cells with miR-340 inhibits myeloma-related angiogenesis.

The study of bone marrow stromal cells (BMSCs) and the exosomes they secrete is considered promising for cancer therapy. However, little is known about the effect of donor age on BMSCs. In the present study, we investigated the therapeutic potential of BMSC exosomes derived from donors of different ages using an in vivo model of hypoxic bone marrow in multiple myeloma (MM).

Genetic variations of bone marrow mesenchymal stromal cells derived from acute leukemia and myelodysplastic syndrome by targeted deep sequencing.

Bone marrow mesenchymal stromal cells (MSCs), which support proliferation and differentiation of hematopoietic stem cells, may play a crucial role in the pathogenesis of myeloid neoplasms. To determine whether MSCs in myeloid neoplasms harbor distinct somatic mutations that may affect their function, we used a targeted gene sequencing panel containing 50 myeloid neoplasm-associated genes with coverage of ≥500. We compared the genetic alterations between MSCs and bone marrow hematopoietic (BM) cells from patients with acute leukemia (n=5) or myelodysplastic syndrome (MDS, n=5).

Ecl1 is a zinc-binding protein involved in the zinc-limitation-dependent extension of chronological life span in fission yeast.

Overexpression of Ecl1-family genes (ecl1 , ecl2 , and ecl3 ) results in the extension of the chronological life span in Schizosaccharomyces pombe. However, the mechanism for this extension has not been defined clearly. Ecl1-family proteins consist of approximately 80 amino acids, and four cysteine residues are conserved in their N-terminal domains.

Downregulation of Plasma miR-215 in Chronic Myeloid Leukemia Patients with Successful Discontinuation of Imatinib.

Approximately 40% of chronic myeloid leukemia (CML) patients who discontinue imatinib (IM) therapy maintain undetectable minimal residual disease (UMRD) for more than one year (stopping IM (STOP-IM)). To determine a possible biomarker for STOP-IM CML, we examined plasma miRNA expression in CML patients who were able to discontinue IM. We first screened candidate miRNAs in unselected STOP-IM patients, who had sustained UMRD after discontinuing IM for more than six months, in comparison with healthy volunteers, by using a TaqMan low-density array for plasma or exosomes.

Exosomal miR-135b shed from hypoxic multiple myeloma cells enhances angiogenesis by targeting factor-inhibiting HIF-1.

Exosomes are small endosome-derived vesicles containing a wide range of functional proteins, mRNA, and miRNA. Exosomal miRNA from cancer cells helps modulate the microenvironment. In multiple myeloma (MM), the massive proliferation of malignant plasma cells causes hypoxia.

The fission yeast php2 mutant displays a lengthened chronological lifespan.

The Schizosaccharomyces pombe php2(+) gene encodes a subunit of the CCAAT-binding factor complex. We found that disruption of the php2(+) gene extended the chronological lifespan of the fission yeast. Moreover, the lifespan of the Δphp2 mutant was barely extended under calorie restricted (CR) conditions.

Extension of chronological lifespan by ScEcl1 depends on mitochondria in Saccharomyces cerevisiae.

Ecl1, a product of the YGR146C gene in Saccharomyces cerevisiae, was identified as a factor involved in chronological lifespan. In this study we found evidence that the function of Ecl1 in the extension of chronological lifespan is dependent on mitochondrial function. The respiratory activity of cells increased when Ecl1 was overexpressed or cells were grown under calorie restriction, but there was no additive effect of calorie restriction and Ecl1 overexpression on increases in respiratory activity or on the extension of chronological lifespan.

Chronological lifespan extension by Ecl1 family proteins depends on Prr1 response regulator in fission yeast.

ecl1+, ecl2+ and ecl3+ genes encode highly homologous small proteins, and their over-expressions confer both H2O2 stress resistance and chronological lifespan extension on Schizosaccharomyces pombe. However, the mechanisms of how these Ecl1 family proteins function have not been elucidated. In this study, we conducted microarray analysis and identified that the expression of genes involved in sexual development and stress responses was affected by the over-expression of Ecl1 family proteins.

hsf1 (+) extends chronological lifespan through Ecl1 family genes in fission yeast.

The heat shock factor (HSF), a protein evolutionarily conserved from yeasts to human, regulates the expression of a set of proteins called heat shock proteins (HSPs), many of which function as molecular chaperones. In Saccharomyces cerevisiae, the HSF binds to the 5' upstream region of YGR146C and activates its transcription. YGR146C encodes a functional homolog of ecl1 (+), ecl2 (+), and ecl3 (+) of Schizosaccharomyces pombe.

Identification and characterization of an Ecl1-family gene in Saccharomyces cerevisiae.

We found that YGR146C of Saccharomyces cerevisiae encodes a functional homolog of Ecl1 that is involved in the chronological lifespan of Schizosaccharomyces pombe. When YGR146C is overexpressed, it extends the viability of wild-type S. cerevisiae cells after entry into the stationary phase, as in the case of Ecl1.

A novel gene, ecl1(+), extends the chronological lifespan in fission yeast.

We have identified a novel gene from Schizosaccharomyces pombe that we have named ecl1(+) (extender of the chronological lifespan). When ecl1(+) is provided on a high-copy number plasmid, it extends the viability of both the Deltasty1 MAP kinase mutant and the wild-type cells after entry into the stationary phase. ecl1(+) encodes an 80-amino acid polypeptide that had not been annotated in the current database.