MCCC2基因变异致3-甲基巴豆酰辅酶A羧化酶缺乏症患儿的家系分析

目的对1例临床疑诊3-甲基巴豆酰辅酶A羧化酶缺乏症(3-methylcrotonyl-coenzyme A carboxylase deficiency,MCCD)患儿及其父母进行基因变异分析,寻找该家系的致病变异,为临床诊断提供分子遗传学依据。方法抽提先证者及其父母的外周血基因组DNA,应用全外显子组基因测序技术对疑似为MCCD疾病的先证者进行致病基因筛查。根据高通量测序结果,对先证者及其父母进行变异位点的Sanger测序验证分析。应用计算机软件预测变异位点氨基酸进化保守性和变异可能导致的蛋白质结构和功能变化,分析变异位点的性质。结果Sanger测序结果显示先证者为MCCC2基因c.1342G>A(p.Gly448Ala)纯合错义变异,为未报道过的新变异。先证者母亲为c.1342G>A(p.Gly448Ala)杂合变异携带者,父亲未检测到该变异。用PolyPhen-2和Mutation Taster软件预测该变异为致病性,变异区域序列在不同物种间高度保守。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南,MCCC2基因c.1342G>A(p.Gly448Ala)变异判定为可能致病性变异(PM2+PP2~PP5)。结论先证者MCCC2基因c.1342G>A(p.Gly448Ala)纯合错义变异是其分子发病机制,基因变异分析有助于明确临床诊断。     

一例酪氨酸羟化酶缺乏症导致的小儿帕金森症伴运动延迟的临床及基因变异分析

目的探讨1例酪氨酸羟化酶缺乏症导致的小儿型帕金森伴运动延迟患儿家系的临床特点,并分析其基因变异情况。方法收集2018年6月就诊郑州大学附属儿童医院的1例酪氨酸羟化酶缺乏症患儿的临床特点,提取患儿及其家系成员外周血DNA,对患儿多巴反应性肌张力不良相关基因三磷酸鸟苷环水解酶1基因(guanosine triphosphate cyclohydrolaseⅠ,GCH1)、酪氨酸羟化酶基因(tyrosine hydroxylase,TH)、墨蝶蛉还原酶基因(sepiapterin reductase,SPR)全部外显子进行深度测序,对变异位点进行分析并通过Sanger测序验证。结果该患儿7月11天,因"翻身不灵活、不会独坐"就诊。运动功能减退,动作延迟,肌张力稍低,肢体僵硬,头有抖动,轻微斜颈,智力发育稍微落后,自3个月大开始有肢体不自主抖动,持续约十几秒自行缓解,情绪激动时和睡前该动作较多。头颅MRI提示双侧额颞部蛛网膜下腔增宽,颞部增宽明显,被误诊为脑性瘫痪。基因变异分析发现其TH基因c.457C>T(p.R153X)无义变异和c.720C>G(p.I240M)错义变异,分别来源于其父亲和母亲,属于复合杂合变异,符合常染色体隐性遗传,其中c.457C>T(p.R153X)为国内外已报道致病变异,c.720C>G(p.I240M)未见报道。结论报告一例1岁以内发病的因酪氨酸羟化酶缺乏症引起的婴儿型帕金森伴运动迟,TH基因变异是导致酪氨酸羟化酶缺乏症的主要原因之一,本研究结果发现的c.720C>G(p.I240M)变异进一步丰富了TH基因的变异谱。     

RRM2B基因复合杂合变异导致的线粒体耗竭综合征家系的临床特征和遗传学分析

目的:探讨1个线粒体DNA耗竭综合征8A型家系的临床特点和致病基因。方法:对患儿进行全外显子测序筛查潜在的基因变异,Sanger测序进行家系验证,并用PolyPhen-2与PROVEAN软件预测氨基酸变异对蛋白功能的影响。结果:患儿,女,2个月4天,临床表现为喂养困难、呼吸急促、肌张力低下等,实验室辅助检查提示患儿发育...     

Early hypothermia as risk factor in severely burned patients: A retrospective outcome study

IntroductionBurn trauma-related hypothermia is a frequent observation but risk factors and impact on patient related outcome are ambiguously reported. It is expected that hypothermia is associated with increased mortality and reduced overall outcome in severely burned patients, but available evidence is limited.MethodsThis retrospective single-center-study reviewed preclinical service protocols and medical records of patients sustaining a burn with a total body surface area (TBSA) ≥15% from 2008 to 2012. General patient and burn specific characteristics, outcome parameters as well as body temperature at admission measured via urine catheter or nasal temperature probe were recorded and statistically analyzed comparing normothermic (≥36 °C), mild hypothermic (<36 °C) and severely hypothermic (<34.5 °C) patients. Chi-square test was performed to demonstrate impact of hypothermia on primary outcome parameters and to reveal risk factors for developing hypothermia. To assess independent influences on mortality, a multivariate logistic regression analysis was performed.ResultsOut of 300 patients matching inclusion criteria, a sufficient record of temperature was found in 144 patients (48%). Out of 141 eligible patients with an average burn extent (SD) of 33.38% (24.5%) TBSA, 31.9% (n = 45) suffered from severe hypothermia (<34.5 °C) and 28.4% (n = 40) showed mild hypothermia. Total burn extent, presence of full thickness burns, presence of inhalation injury, preclinical mechanical ventilation and administration of sedative drugs were risk factors for developing hypothermia. Patients’ age, total burn extent and presence of full thickness burns could be identified as independent factor for mortality. Although a trend towards an independent positive influence of normothermia at admission on mortality was seen, it was not statistically significant.ConclusionIncidental hypothermia of burned patients is associated with an increased mortality and needs to be addressed by emergency health care providers and immediately at the burn center. Especially patients with extensive burns, full-thickness burns, inhalation injury or patients undergoing preclinical intubation are at risk for hypothermia and benefit from any measures for temperature preserving.     

Nonprofessional phagocytosis in trophectoderm cells of human preimplantation blastocysts

Trophoblast phagocytosis has been considered important in pregnancy. However, whether human preimplantation blastocysts possess phagocytic activity is still unclear. In this study, we determined the phagocytosis potential in human trophectoderm cells of blastocysts prior to implantation. Fluorescent microspheres were used as markers for phagocytic analysis under transmission electron microscope (TEM) and fluorescence microscopy. Phagocytosis of 1 μm fluorescent microspheres was observed in most (9/11) day-6 and even some (2/9) day-5 blastocysts. More effective phagocytosis occurred in blastocysts at the morula-blastocyst stage of day-6. Furthermore, we observed an increased trend of phagocytic acitivities in polar trophectoderm. Our findings indicated phagocytic ability exists in human blastocysts prior to implantation and the differentiation between polar and mural trophectoderm may be associated with blastocyst implantation.

Abbreviations: TEM: transmission electron microscope; ZP: zona pellucida; PGD: preimplantation genetic diagnosis; ICM: inner cell mass; FGF4: fibroblast growth factor 4     

Are refugees arriving in Denmark an under-immunised group for measles? A cross-sectional serology study

BackgroundIn 2018, Europe faced the highest number of Measles cases in a decade. In Denmark, the childhood vaccination programme has a coverage of approximately 90%. To eliminate the disease, vaccine coverage needs to be above the herd immunity threshold of 95%. This can be even more difficult to obtain, when vaccination programmes break down due to war, natural disasters etc. and concern has been raised, that unvaccinated refugees could facilitate spread of measles when migrating.MethodsIn order to address this concern, we tested 513 newly arrived refugees and family reunified refugees aged between 0 and 70 years for measles IgG antibodies. The participants were tested as part of a general health assessment between May 2016 and October 2018. In the cohort, 50% were males and the majority came from Syria (55%).ResultsWe found that 85% of the total group of refugees had immunity against measles. The 15% lacking antibodies were evenly distributed between the various countries of origin. Moreover, we found immunity to increase with age, leaving young children most vulnerable to infection, 79.9% (<19 years) vs 89.1% (≥19 years). Interview questions on previous vaccinations did not correlate to serology.ConclusionRefugees have measles immunity slightly lower than the host population.     

The landscape of international oral and maxillofacial surgery collaborations from 1996 to 2020: a scoping review of the published literature

The emerging field of global oral and maxillofacial surgery (OMS) aims to improve worldwide access to safe, timely, and affordable OMS care. However, there exists a dearth of literature thoroughly detailing the scope of academic global OMS collaborations between high-income countries (HICs) and low- and/or lower middle-income countries (LICs/LMICs). This scoping review was performed to characterize the landscape of global academic OMS collaborations between HICs and LICs/LMICs. A five-stage methodological framework was used. Academic global OMS collaborations from 1996 to 2020 were identified via an electronic database and grey literature review. A total 1318 articles were identified on December 17, 2020. Following the application of inclusion and exclusion criteria, 71 articles describing 81 unique global OMS academic collaborations were included in the final analysis. The most common HIC was the United States (44.4%); the majority of LIC/LMICs were within Africa (45.8%). Of the total interventions, 89.6% improved LIC/LMIC capacity development, and surgical (43.8%) interventions were the most common. By serving as a central report on current and past academic collaborations in global OMS, this review helps identify areas in need of surgical capacity building, lays the foundation for future research efforts on the topic, and serves as a resource for individuals aiming to become involved in global OMS.     

罕见亚型大疱性表皮松解症3例及家系调查

【摘要】 目的 报道3例罕见亚型遗传性大疱性表皮松解症（EB）。方法 收集先证者及其亲属的临床资料,全外显子测序筛查先证者致病基因,采用Sanger或qPCR测序对患者及其亲属进行突变验证。结果 例1表现为背部线状红色瘢痕,患者及有相似临床表现的母亲、无症状女儿均携带COL7A1基因c.4573G>A（p.Gly1525Arg）突变。例2表现为全身网状色素沉着,偶伴手足水疱,携带KRT5基因c.74C>T（p.Pro25Leu）新发突变。例3表现为曝光部位为主的色素异常伴左手不完全并指,先证者携带FERMT1基因2-6号外显子纯合缺失突变,分别来自无症状父母。例1诊断为显性痒疹型营养不良型 EB, 例2诊断为斑驳色素型单纯型EB, 例3诊断为Kindler EB。结论 EB临床异质性高,基因检测对于罕见亚型EB的明确诊断非常重要。