假肥大型肌营养不良症产前诊断与遗传咨询

<正> 假肥大型肌营养不良症(pseudohypertrophic muscular dystrophy)是由于基因缺陷引起的疾病,以进行性肌肉萎缩与肌无力为主要特征,分Duchenne型(Duchenne muscular dystrophy,DMD)和Becker型(Becker muscular dystrophy,BMD)。DMD是假肥大型肌营养不良症中最常见和最严重的类型,发病率为活产男婴的1/3500,多数于12～13岁前丧失行走能力,20岁左右死亡。BMD发病率约1/30000,临床症状体征较轻,进展缓慢,14岁后仍能行走。DMD/BMD是最常见的X连锁隐性致死性遗传病之一,至今缺乏有效的治疗方法,只有通过产前诊断阻止患病胎儿出生以达到遗传优生的目的。     

肌营养不良蛋白在假肥大肌营养不良双生子肌组织中的表达

[目的]假肥大肌营养不良是男性最常见的X-连锁隐性遗传病,而肌营养不良蛋白(dystrophin)在DMD患者肌细胞上的表达异常是导致该病发生的最根本的病理生理机制。[方法]应用兔抗Anti5-7多克隆抗血清及免疫组化技术检测dystrophin在两对DMD孪生子肌组织中的表达。[结果]显示dystrophin在无症状的孪生子肌组织中存在着阳性表达,而在DMD患儿肌组织中则表达缺失。[结论]检测肌细胞膜上dystrophin蛋白的表达对DMD患者的诊断及预后判定有着重要的应用价值。     

假肥大型肌营养不良症的优生咨询

<正> 假肥大型肌营养不良症(Duchenne DMD)是一种致死性的X连锁隐性遗传病。该病发病率高,占活产男婴的1/3 500～4000,群体中携带本病基因的频率为1/2 300。临床特征是机体多部位骨骼肌进行性无力、萎缩,腓肠肌假性肥大。幼儿期即可发病,病程进展快,多在20岁左右死亡。目前尚无有效的治疗方法,因此开展优生咨询,进行女性携带者的检出和产前诊断是预防DMD患儿发生的关键。现将DMD的优生咨询作一介绍。     

MLPA技术在假肥大型肌营养不良症基因检测和产前诊断中的应用

目的 评价多重连接依赖式探针扩增 (Multiplex ligation-dependent probe amplification,MLPA) 技术对假肥大型肌营养不良症(DMD)患者进行基因诊断和产前诊断的应用价值。方法 应用MLPA技术对具有典型表型的22例患者进行DMD基因79个外显子拷贝数变异(缺失/重复突变)检测,同时对部分家系中孕妇携带者进行产前诊断,STR毛细管电泳连锁分析方法进行辅助诊断及验证。结果 22例患者中15例为缺失突变,4例为重复突变,3例未见拷贝数变异。14例MLPA检测结果为阳性的患者母亲中有9例为携带者。产前诊断的7例胎儿中,3例为女性胎儿携带者,3例男性正常胎儿和1例女性正常胎儿。结论 MLPA技术能准确、快速、可靠地检测DMD基因拷贝数变异(缺失或重复突变)。     

携带者发病的进行性肌营养不良症一家系分析

假肥大型进行性肌营养不良症 ,是一种性连锁隐性遗传性疾病 ,一般可分为Duchenne肌营养不良 (DMD)和Becker肌营养不良 (BMD)两种类型。DMD发病率约占活产男婴 1/ 3 5 0 0 ,表现为进行性肌肉萎缩无力 ,多数于 12岁前不能行走 ,2 0岁左右死亡。BMD的发病率约为前者的 1/ 10 ,症状较缓和[1] 。近年有较多关于女性BMD患者的报道 ,亦有研究发现 ,DMD致病基因携带者 (女性 )表现肢体轻微无力、肌酶轻微升高 ,但尚未见有典型临床表现的假肥大型进行性肌营养不良的DMD致病基因携带者[2 ] 。笔者在一DMD家系中诊治 1例 ,现报道如下。1　临…     

面肩肱型肌营养不良症一个家系13例临床分析

进行性肌营养不良症是一组原发于肌肉的遗传性变性疾病,主要特点为进行性加重的肌肉萎缩和无力。面肩肱型为其中一类型。我科收治1例,发现一个家系13例发病,临床少见。报告如下。 1 临床资料此家系中发病年龄最早9岁,最迟30岁,平均20.3岁。共13例患者症状与体征相似。起病隐袭,面部表情肌最早受累,上险稍下垂,额纹和鼻唇沟消失,表情运动微弱或消失,口轮匝肌假性肥大,嘴唇厚而微翘,口眼闭合均无力,不能促眉、皱额、鼓气等。有肩胛带肌受累,冈上肌、岗下肌、菱形肌、前锯肌、三角肌、肱二头肌、肱桡肌均有不同程度的萎缩。上     

Duchenne型肌营养不良症二家系报告

Duchenne型肌营养不良症(Duchenne muscular dystrophy,DMD)是较常见的X性连锁隐性遗传病。在临床观察30例中,有家族史12例,现将有特点的2家系报告如下。 患儿1 男 6岁 因走路不稳易摔倒4年,起床费力2年就诊。患儿足月顺产,1岁会走,步态不稳,2岁时走路似鸭步态,常摔跤,4岁时发现双小腿变粗,但起床费力,必先俯卧,然后用双手撑地、扶双足、膝、大腿才     

进行性肌营养不良症携带者基因诊断的研究

进行性肌营养不良是一类发病率较高的性连锁隐性遗传病。由于患者不可治愈,防范此病的重点在于筛查携带者和对妊娠妇女进行产前诊断。发展多种技术针对营养不良(dystro-phin)基因不同突变类型进行检测及排除正常X染色体遮蔽的干扰是女性携带者诊断的关键,近年来随着分子生物学技术的发展,进行性肌营养不良症携带者的基因诊断方法和技术取得了一定的进展。     

Duchenne型肌营养不良症的植入前遗传学诊断

植入前遗传学诊断是在胚胎着床前对其遗传物质进行分析,结合体外受精和胚胎移植技术,选择正常的胚胎进行移植的一门新兴的辅助生殖技术,该技术在遗传病的诊断中占有越来越重要的地位。截至到2005年10月世界上已有1959例正常婴儿通过植入前诊断技术诞生。总结Duchenne型肌营养不良症植入前遗传学诊断的步骤和各项技术,并对其目前存在的问题和解决方法以及其应用前景进行讨论。     

Deriving a Preference-Based Measure for People With Duchenne Muscular Dystrophy From the DMD-QoL

ObjectivesThis study generates a preference-based measure for capturing the quality of life of people with Duchenne muscular dystrophy (DMD) from a new measure of quality of life, DMD-QoL.MethodsA health state classification system was derived from the DMD-QoL based on psychometric performance of items, factor analysis, and item response theory analysis. Preferences for health states described by the classification system were elicited using an online discrete choice experiment survey with life years as an additional attribute, from members of the UK general population (n = 1043). Discrete choice experiment data was modeled using a conditional fixed-effects logit model and utility estimates were directly anchored on the 1 to 0 full health-dead scale.ResultsThe health state classification system has 8 dimensions: mobility, difficulty using hands, difficulty breathing, pain, tiredness, worry, participation, and feeling good about yourself. The standard model had mostly statistically significant coefficients and reflected the instrument’s monotonic structure. However, 2 dimensions had inconsistent coefficients (where utility increased as health worsened) and a consistent model was estimated that merged adjacent inconsistent severity levels. The best state defined by the classification system has a value of 1 and the worst state has a value of −0.559.ConclusionThe modeled results enable DMD-QoL-8D utility values to be generated using DMD-QoL or DMD-QoL-8D data to generate QALYs for people with DMD. QALYs can then be used to inform economic models of the cost-effectiveness of interventions in DMD. Future research comparing the psychometric performance of DMD-QoL-8D to existing generic preference-based measures, including EQ-5D-5L, is recommended.     

Duchenne型肌营养不良症的临床特点和基因分析

目的探讨Duchenne型肌营养不良症(DMD)的临床特点和基因特点,为临床诊断提供依据。方法回顾性分析2015—2019年中山大学附属第六医院遗传代谢实验室基因检测确诊的15例DMD患儿的基因检测结果和临床资料,探讨DMD的临床特征和基因特点。结果 15例患儿发病年龄1个月～12岁,临床表现以小腿腓肠肌假性肥大、Gowers征及走路摇摆(鸭步)为主,AST、ALT、CK、CK-MB及肌红蛋白等肌酶水平均明显升高。通过组合的高通量检测技术等检查DMD基因情况,结果多为缺失突变,共12例(80.0%),其中大片重复缺失突变10例(66.7%),点突变2例(13.3%);错义突变1例(6.6%);插入突变1例(6.6%);无义突变1例(6.6%)。其中7例(46.7%)患儿母亲进行了相关基因检测,4例患儿母亲为该基因突变点携带者。而根据ACMG变异类型,15例患儿中13例(86.7%)为致病突变,2例(13.3%)为疑似致病突变。同时15例病例中有2例暂无相关文献报道过。所有的突变可发生在基因的任何位置,但缺失的热点区域位于基因的中央区外显子45～55区共8例,占缺失突变的53.3%。结论...     

Hepatic Steatosis Assessment as a New Strategy for the Metabolic and Nutritional Management of Duchenne Muscular Dystrophy

Growing evidence suggests that patients with Duchenne muscular dystrophy (DMD) have an increased risk of obesity and metabolic syndrome (MetS). The aim of this study was to investigate the potential risk factors for MetS and hepatic steatosis in patients with different stages of DMD. A total of 48 patients with DMD were enrolled and classified into three stages according to ambulatory status. Body mass index (BMI), serum fasting glucose, insulin, and lipid profiles including triglycerides (TG) and high-density lipoprotein were measured, and the homeostatic model assessment for insulin resistance (HOMA-IR) index was evaluated. Ultrasound examinations of the liver were performed to assess hepatic steatosis using the Nakagami parameter index (NPI). The results showed that BMI, TG, HOMA-IR, and ultrasound NPI differed significantly among DMD stages (p < 0.05). In contrast to the low rates of conventional MetS indices, including disturbed glucose metabolism (0%), dyslipidemia (14.28%), and insulin resistance (4.76%), a high proportion (40.48%) of the patients had significant hepatic steatosis. The ultrasound NPI increased with DMD progression, and two thirds of the non-ambulatory patients had moderate to severe hepatic steatosis. Steroid treatment was a risk factor for hepatic steatosis in ambulatory patients (p < 0.05). We recommend that DMD patients should undergo ultrasound evaluations for hepatic steatosis for better metabolic and nutritional management.     

抗肌萎蛋白缺陷型肌营养不良症25例临床和病理研究

目的探讨两种类型的抗肌萎蛋白(dystrophin)缺陷型肌营养不良症的临床表现、电生理和病理特点。方法根据dystrophin免疫组化染色,将25例肌营养不良患儿分为Duchenne型(DMD)和Becker型(BMD),各为11例和14例。对其临床、电生理和病理学特点进行对比分析。结果DMD发病年龄为(3.9±1.15)岁,磷酸肌酸激酶(CK)升高30～126倍,dystrophin完全缺失;BMD为(7.2±3.38)岁和2～35倍,dystrophin部分缺失。两型肌电图为肌源性损害,在光镜都有肌纤维变性坏死、opacqe肌纤维,结缔组织增生,吞噬和再生现象。透射电镜可观察到肌丝排列紊乱、肌浆网扩张、线粒体肿胀、肌浆膜缺损,肌原纤维溶解坏死、Z线排列紊乱等;但DMD损伤较BMD重。结论DMD和BMD都是抗肌萎蛋白缺陷所致,DMD的临床症状和病理改变都较BMD重。     

Nutraceutical Screening in a Zebrafish Model of Muscular Dystrophy: Gingerol as a Possible Food Aid

Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is an inherited neuromuscular disorder that causes loss of muscle mass and motor skills. In the era of genomic medicine, there is still no known cure for DMD. In clinical practice, there is a growing awareness of the possible importance of nutrition in neuromuscular diseases. This is mostly the result of patients’ or caregivers’ empirical reports of how active substances derived from food have led to improved muscle strength and, thus, better quality of life. In this report, we investigate several nutraceutical principles in the sapje strain of zebrafish, a validated model of DMD, in order to identify possible natural products that, if supplemented in the diet, might improve the quality of life of DMD patients. Gingerol, a constituent of fresh ginger, statistically increased the locomotion of mutant larvae and upregulated the expression of heme oxygenase 1, a target gene for therapy aimed at improving dystrophic symptoms. Although three other compounds showed a partial positive effect on locomotor and muscle structure phenotypes, our nutraceutical screening study lent preliminary support to the efficacy and safety only of gingerol. Gingerol could easily be proposed as a dietary supplement in DMD.     

In and On their Own Terms: Children and Young People's Accounts of Life with Duchenne Muscular Dystrophy

Semi-structured interviews were conducted with boys and young men who have Duchenne muscular dystrophy (DMD), a severe, degenerative condition that only affects boys. The main focus of the interviews was to explore how the participants thought they might make a decision to take part in medical research. To better understand this, aspects of the participants’ lives were discussed; they talked about the impact of discomfort and declining mobility, and the social issues they experienced, such as discrimination and a sense of difference. Their observations indicate that living with a degenerative condition has physical and social impacts, and that there are limited opportunities for them to talk about these issues. It was also apparent that parents are key figures who provide care for their child, often in the absence of comprehensive support services. Raising these matters privileges the experiences of severely disabled children and young people, who live with increasing muscle weakness, disablist attitudes and intensifying support needs. Their contributions build on understandings of life with a degenerative condition, highlighting the intersection of impairment and social issues in their lived experience.     

6～11岁杜氏进行性肌营养不良儿童与正常儿童下肢肌力对照分析

目的 比较6～11岁杜氏进行性肌营养不良(DMD)患儿与正常儿童下肢肌力差异,为开展DMD患儿的肌力训练提供科学依据。方法 2015年4月-2017年4月选择DMD患儿和正常儿童各20例,其中DMD患儿男19例,女1例;正常组男18例,女2例,两组儿童平均年龄均为(9.0±1.7)岁。采用手持式肌力测定仪(HHD)测定下肢髋、膝、踝等部位肌群肌力,比较DMD与正常儿童下肢肌群间及不同年龄间的肌力差异。结果 DMD组下肢肌力除足跖屈肌群以外均明显弱于正常组(P＜0.05);DMD组中6岁～组和9～11岁组各组肌群肌力差异无统计学意义(P＞0.05);在6岁～组中DMD患儿双侧髋外展和足趾屈肌力与正常组差异无统计学意义(P＞0.05),DMD组足趾屈肌力甚至高于正常儿童; 9～11岁组中DMD患儿除足趾屈肌群外髋屈曲、髋伸展、髋外展、膝屈曲、膝伸展和踝背屈肌群肌力都已经显著落后于正常儿童(P＜0.05)。结论 DMD患儿下肢肌群除足跖屈肌外均明显低于正常组儿童。开展DMD患儿下肢力量训练应关注所有肌群,在较大年龄组尤其需要重视髋膝伸展肌群。