Case Report: Novel compound heterozygous TPRKB variants cause Galloway-Mowat syndrome

BackgroundGalloway-Mowat syndrome (GAMOS) is a rare genetic disease characterized by early-onset nephrotic syndrome and microcephaly with central nervous system abnormalities. Pathogenic variants in genes encoding kinase, endopeptidase, and other proteins of small size (KEOPS) complex subunits cause GAMOS. The subunit TPRKB (TP53RK binding protein) has been reported in only two patients with GAMOS with homozygous missense variants.Clinical reportHerein, we described a three-year-old male with GAMOS. He exhibited developmental delay, developmental regression, microcephaly, distinctive facial features, skeletal abnormalities, and epilepsy. Brain magnetic resonance imaging revealed progressive brain atrophy, delayed myelination, T2-hypointense signals in the thalamus, and multiple intracranial abnormal signals on diffusion-weighted imaging. He presented with relapsing nephrotic proteinuria exacerbated by upper respiratory tract infections and progressive renal function decline. Exome sequencing identified compound heterozygous missense and frameshift variants in TPRKB: c.224dup, p.(Ser76IlefsTer3) and c.247C>T, p.(Leu83Phe).ConclusionsOur study supports that pathogenic TPRKB variants cause KEOPS complex-related GAMOS

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia Patients with Central Nervous System Involvement

AbstractCentral nervous system (CNS) involvement in adult acute myeloid leukemia (AML) is rare and associated with poor outcomes. Therefore, CNS involvement in AML is an indicator for allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the impact of CNS involvement in AML on the outcome of allo-HSCT remains unclear. We performed a large-scale nationwide retrospective analysis to elucidate the outcomes of allo-HSCT on AML with CNS involvement (CNS+AML). Clinical data were collected from a registry database of the Japan Society for Hematopoietic Cell Transplantation. CNS involvement was defined as the infiltration of leukemia cells into the CNS or myeloid sarcoma in the CNS identified at any time from diagnosis to transplantation. One hundred fifty-seven patients with CNS+AML underwent allo-HSCT between 2006 and 2011. The estimated overall survival, cumulative incidence of relapse and nonrelapse mortality at 2 years for CNS+AML (51.2%, 30.2%, and 14.5%, respectively) were comparable with those for AML without CNS involvement (48.6%, 27.4%, and 22.0%, respectively). Univariate and multivariate analyses indicated that the development of chronic graft-versus-host disease, disease status, and cytogenetic risk category were independent prognostic factors for overall survival for CNS+AML. These results suggest that allo-HSCT may improve outcomes in patients with CNS+AML

豆類の脱湿・吸湿時における挙動について

The changes in water contents of adzuki beans, cowpeas, toramames (a variety of kidney bean) and soybeans during removal and absorption of moisture were investigated to clarify the effect of humidity on behavior of beans. It was found that dehumidified adzuki beans hardly absorbed moisture even if they were put in the overhumid circumstance for a long time and the dehumidification of adzuki beans occurred through hilum. Beans other than adzuki beans absorbed more moisture than the original water content by addition of moisture after dehumidification. Adzuki beans were used as the stuff for packing into pillow in Japan till recent years. This suggests that the characteristics on dehumidification and humidification of adzuki beans were utilized for the material

Acute megakaryoblastic leukemia, unlike acute erythroid leukemia, predicts an unfavorable outcome after allogeneic HSCT

Acute erythroid leukemia (FAB-M6) and acute megakaryoblastic leukemia (FAB-M7) exhibit closely related properties in cells regarding morphology and the gene expression profile. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the mainstay of the treatment for both subtypes of leukemia due to their refractoriness to chemotherapy and high rates of relapse, it remains unclear whether allo-HSCT is curative in such cases due to their scarcity. We retrospectively examined the impact of allo-HSCT in 382 patients with M6 and 108 patients with M7 using nationwide HSCT data and found the overall survival (OS) and relapse rates of the M6 patients to be significantly better than those of the M7 patients after adjusting for confounding factors and statistically comparable with those of the patients with M0/M1/M2/M4/M5 disease. Consequently, the factors of age, gender, performance status, karyotype, disease status at HSCT and development of graft-vs.-host disease predicted the OS for the M6 patients, while the performance status and disease status at HSCT were predictive of the OS for the M7 patients. These findings substantiate the importance of distinguishing between M6 and M7 in the HSCT setting and suggest that unknown mechanisms influence the HSCT outcomes of these closely related subtypes of leukemia. © 2016 Elsevier Ltd.Embargo Period 12 month

Ideal Body Shape in Young Japanese Women and Assessment of Excessive Leanness Based on Allometry

The present study is aimed to clarify the degree of leanness desired by contemporary young Japanese women using questionnaires and to use allometry to define the bodyweight boundary between the excessively lean and the others for a given height. Questionnaires on ideal body shape weredistributed to female college students living in Akita and the suburbs of Tokyo. Data for 578 respondents, aged 18 to 21years-old, were analyzed. The questionnaire asked the subjects to report their current and ideal body shape and to make aqualitative self-assessment of their weight. On average, the perceived ideal weight was 5.2 kg lower than the current weight. The results also revealed that young women have atendency to misunderstand their body shape and to regard themselves as heavier than they really were. Meanwhile, we defined leanness as a state of insufficient lean body mass (LBM, kg) in relation to height (Ht, cm). Allometric equation of LBM on Ht and the standard error of estimate (SEE) werecalculated as LBM=3.87X 10-3XHt1826 and 1.09, respectively.The LBM boundary between the excessively lean and the others was determined using these values according to a statistical procedure comparing normal and abnormal values.The corresponding total body weight was estimated from the boundary LBM in the literature. Subsequently the body weightboundary for each height was tabulated in order to make young women reconsider weight control. The subjects were asked toassess the body weight boundary for their own height. The boundary values were found to be consistent with the sense of the subjects. J Physiol Anthropol 22 (2): 105-110, 2003http://www.jstage.jst.go.jp/en

Adult-onset Repeat Rhabdomyolysis with a Very Long-chain Acyl-CoA Dehydrogenase Deficiency Due to Compound Heterozygous <i>ACADVL</i> Mutations

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a genetic disorder of fatty acid beta oxidation that is caused by a defect in ACADVL, which encodes VLCAD. The clinical presentation of VLCAD deficiency is heterogeneous, and either a delayed diagnosis or a misdiagnosis may sometimes occur. We herein describe a difficult-to-diagnose case of the muscle form of adult-onset VLCAD deficiency with compound heterozygous ACADVL mutations including c.790A>G (p.K264E) and c.1246G>A (p.A416T)

Effect of Resistant Starch on the Gut Microbiota and Its Metabolites in Patients with Coronary Artery Disease

Aim: Bacteroides vulgates and B. dorei have a protective effect against atherosclerosis, suggesting that expansion of these species in the gut microbiota could help patients with coronary artery disease (CAD). This study aimed to investigate the effect of resistant starch (RS) on the gut microbiota and its metabolites in fecal sample cultures from patients with CAD and individuals without CAD, using a single-batch fermentation system. Methods: Fecal samples from 11 patients with CAD and 10 individuals without CAD were fermented for 30 h with or without RS in the Kobe University Human Intestinal Microbiota Model (KUHIMM). Gut microbiota and the abundance of B. vulgatus and B. dorei were analyzed using 16S ribosomal ribonucleic acid (rRNA) gene sequencing and the quantitative polymerase chain reaction. Short-chain fatty acids were analyzed using high-performance liquid chromatography. Results: Gut microbial analysis showed significantly lower levels of B. vulgatus and B. dorei in the original fecal samples from patients with CAD, which was simulated after 30 h of fermentation in the KUHIMM. Although RS significantly increased the absolute numbers of B. vulgatus and B. dorei, and butyrate levels in CAD fecal sample cultures, the numbers varied among each patient. Conclusions: The effect of RS on gut microbiota and its metabolites in the KUHIMM varied between CAD and non-CAD fecal sample cultures. The KUHIMM may be useful for preclinical evaluations of the effects of RS on the gut microbiota and its metabolites