Disseminated tuberculosis with paradoxical reactions caused by a Mycobacterium tuberculosis strain belonging to the Indo-Oceanic lineage: An imported case in Japan

Tuberculosis remains a major public health concern. Millions of tuberculosis cases and associated deaths have been reported worldwide. The Indo-Oceanic lineage Mycobacterium tuberculosis is common in Southeast Asia and causes extrapulmonary lesions. Only a few case studies on this lineage with genetic analysis using whole-genome sequencing have been reported in the literature. We present a case of disseminated tuberculosis, characterized by a variety of extrapulmonary lesions and paradoxical reactions, caused by the Indo-Oceanic lineage M. tuberculosis in a woman in Myanmar. A 22-year-old Burmese woman had arthritis in the right knee, with unknown aetiology, and was referred to our hospital. Computed tomography of the trunk revealed multiple nodular shadows in both lungs; swollen mediastinal lymph nodes; and small, low-density areas in the spleen. M. tuberculosis was detected in the sputum sample, joint aspirate, subcutaneous tumor, and exudate. She experienced a variety of paradoxical reactions together with aggressive tuberculosis dissemination in all areas of the body. Whole-genome sequencing of the DNA of MTB obtained from sputum and the right cervical subcutaneous abscess confirmed the Indo-Oceanic lineage of M. tuberculosis, the predominant strain in Myanmar. The Indo-Oceanic lineage M. tuberculosis causes disseminated tuberculosis all over the body including the periungual region. When patients show unusual symptoms, physicians should consider the introduction of new strains from foreign countries. Genetic analyses of the strains are recommended to define and confirm the lineages.     

基于16S rRNA技术研究电针对动脉粥样硬化兔动脉斑块及肠道菌群科水平的影响

目的:观察电针防治干预对动脉粥样硬化(AS)动脉斑块及科水平肠道菌群结构特征的影响,筛选特征性菌群,探析电针抗AS的机制。方法:实验兔平均随机分为空白组、模型组、防治组,每组6只。模型组以高脂饲料结合颈总动脉球囊损伤术方法造模;防治组先予电针干预后造模,后再予电针干预。观察油红O染色、16S rRNA测序与生信分析结果。结果:防治组颈动脉内壁沉积脂质斑块明显少于模型组;空白组与防治组组间肠道菌群群落差异更小;防治组S24-7、Synergistaceae、Veillonellaceae、[Mogibacteriaceae]科菌群相对丰度与模型组比较,差异有统计学意义(P<0.05,P<0.01),与空白组相近。结论:AS与肠道菌群结构变化有关,电针能抑制动脉斑块形成并调整肠道菌群结构,可能与S24-7 Veillonellaceae、[Mogibacteriaceae]科菌群相对丰度有关。     

Novel strategies for rapid identification and susceptibility testing of MRSA

ABSTRACT

Introduction

Methicillin-resistant Staphylococcus aureus (MRSA) is associated with adverse clinical outcomes and increased morbidity, mortality, length of hospital stay, and health-care costs. Rapid diagnosis of MRSA infections has been associated with positive impact on clinical outcomes.     

A male case with CDKL5-associated encephalopathy manifesting transient methylmalonic acidemia

Mutations in the X-linked gene CDKL5 cause early-onset epileptic encephalopathy and severe developmental delay. Because this disorder predominantly affects females, the full clinical spectrum of male patients remains elusive. We herein report a 16-year-old boy, who suffered from intractable seizures 20 days after birth. Serial electroencephalograms detected recurrent focal epileptiform discharges from age 4 months, which evolved to hypsarrhythmia later in infancy. Mass-spectrometric analyses revealed increase in urinary excretion of methylmalonic acid without perturbed concentrations of propionic acid, homocystein and methionine. Whole-exome sequencing identified a de novo, truncating mutation in CDKL5 (NM_003159.2:c.419dupA, p.Asn140Lysfs*8). Targeted sequencing excluded concomitant mutations in methylmalonic academia-associated genes. No methylmalonic acidemia has been reported in children with CDKL5 disorder. Extensive analyses on organic acid metabolism for males with CDKL5 mutations will gain more insight into their biochemical profiles in infancy.     

Massively parallel sequencing on human cleavage-stage embryos to detect chromosomal abnormality

Purpose

Next-generation sequencing technology like MPS has recently been introduced to perform comprehensive chromosome screening on human trophectoderm samples for preimplantation embryo assessment. However, the potential of MPS in chromosome analysis of single cell from blastomeres has not yet been investigated.

Uncommon runs of homozygosity disclose homozygous missense mutations in two ciliopathy-related genes (SPAG17 and WDR35) in a patient with multiple brain and skeletal anomalies

We describe a patient severely affected with multiple congenital anomalies, including brain malformations and skeletal dysplasia suggestive of cranioectodermal dysplasia (CED) ciliopathy, who unusually carries several homozygosity tracts involving homozygous missense mutations in SPAG17 (exon 8; c.1069G > C; p.Asp357His) and WDR35 (exon 13; c.1415G > A; p.Arg472Gln) as revealed by homozygosity mapping and next generation sequencing. SPAG17 is essential for the function and structure of motile cilia, while WDR35 belongs to the same intraflagellar transport (IFT) gene family whose protein products are part of functional IFT A and B complexes. Formerly, SPAG17 was related – through polymorphic variants – to an influence on individuals’ height; more recently, Spag17?/? mice models were reported to present skeletal and bone defects, reduced mucociliary clearance, respiratory distress, and cerebral ventricular enlargement. Homozygous or compound heterozygous mutations in WDR35 have mainly been related to CED2 or short-rib thoracic dysplasia 7, with only three cases showing some brain anomalies. Given that our patient presents these clinical features and the close functional relationship between SPAG17 and WDR35, it is feasible that the combined effects from both mutations contribute to his phenotype. To our knowledge, this patient is the first to harbor a likely pathogenic homozygous mutation in both genes at the same time. Thus, the resulting complex phenotype of this patient illustrates the heterogeneity associated with ciliopathies and further expands the clinical and mutational spectrum of these diseases. Finally, we highlight the combined use of high-throughput tools to diagnose and support the proper handling of this and other patients.     

Arthrogryposis and pterygia as lethal end manifestations of genetically defined congenital myopathies

Arthrogryposis multiplex congenita affects approximately 1 in 3,000 individuals of different ethnic backgrounds and displays an equal incidence in males and females. The underlying mechanism for congenital contracture of the joints is decreased fetal movement during intrauterine development. This disorder is associated with over 400 medical conditions and 350 known genes that display considerable variability in phenotypic expression. In this report, four fetal or perinatal autopsy cases of arthrogryposis were studied by gross morphology, microscopic histopathologic examination, and whole genome sequencing of postmortem DNA. Two stillborn sibling fetuses with arthrogryposis, pterygia, and amyoplasia had compound heterozygous pathogenic variants in NEB. A neonate with a histopathologic diagnosis of nemaline myopathy had a heterozygous de novo pathogenic variant in ACTA1. Another stillborn infant with pterygia and arthrogryposis had a heterozygous de novo likely pathogenic variant in BICD2. These cases demonstrate the utility of whole genome sequencing as the principal diagnostic method of lethal forms of skeletal muscle disorders that present with arthrogryposis and muscle amyoplasia/hypoplasia. Molecular diagnosis provides an opportunity for studying patterns of inheritance and for family counseling concerning future pregnancies.

     

严重创伤患者急救的全程优化护理

目的:探讨全程优化护理在严重创伤患者急救中的临床价值。方法:选择2015年3月至2016年2月南通大学附属医院急诊收治的44例严重创伤患者为研究对象,随机分为观察组和对照组,各22例。观察组患者采用全程优化护理,对照组接受常规急救护理,两组患者排除基础性疾病,对比两组患者的护理效果。结果:观察组患者住院时间短于对照组[(10.4±4.1)d vs(20.7±6.6)d],差异有统计学意义(P0.05);观察组患者和家属满意度优于对照组(100%vs 76.5%)。结论:全程优化护理按照流程进行急救,有利于构建快捷、高效的救治链,提高严重创伤患者的救治效果。     

Single suture craniosynostosis: Identification of rare variants in genes associated with syndromic forms

We report RNA‐Sequencing results on a cohort of patients with single suture craniosynostosis and demonstrate significant enrichment of heterozygous, rare, and damaging variants among key craniosynostosis‐related genes. Genetic burden analysis identified a significant increase in damaging variants in ATR, EFNA4, ERF, MEGF8, SCARF2, and TGFBR2. Of 391 participants, 15% were found to have damaging and potentially causal variants in 29 genes. We observed transmission in 96% of the affected individuals, and thus penetrance, epigenetics, and oligogenic factors need to be considered when recommending genetic testing in patients with nonsyndromic craniosynostosis.