BACKGROUND & AIMS: :In this article, we review the clinical, neuropathological and genetic aspects of distal spinal-muscular atrophy 1 (DSMA1; MIM#604320), formerly designated as autosomal recessive spinal muscular atrophy with respiratory distress type 1 (SMARD1) and also known as distal hereditary-motor neuropathy type 6 (dHMN6 or HMN6).

背景与目标： ：在本文中，我们回顾了远端脊髓性肌肉萎缩症1（DSMA1; MIM＃604320）的临床，神经病理学和遗传学方面，该疾病以前被称为常染色体隐性隐性脊髓性肌肉萎缩症，伴有呼吸窘迫1型（SMARD1），也被称为远端遗传性运动神经病6型（dHMN6或HMN6）。

BACKGROUND & AIMS: BACKGROUND:Left ventricular hypertrabeculation (LVHT) has not been described in myotonic dystrophy Type I (MD1) before. CASE REPORT:A 42-year-old man developed typical features of MD1 since 1992. Creatinekinase was slightly, but recurrently elevated. Needle electromyograms were myogenic and showed extensive spontaneous activity. Muscle biopsy was compatible with MDI. DNA analysis revealed a heterozygous 300 CTG-repeat expansion in the myotonic-dystrophy proteinkinase gene on chromosome 19q13.3. Cardiac history and clinical cardiologic examination were normal. On ECG, ST elevation and atrial flutter were found. The AECG was normal except for atrial flutter. Surprisingly, transthoracic echocardiography revealed LVHT, previously described only in Becker's muscular dystrophy, mitochondriopathies, and Barth syndrome. CONCLUSION:A rare cardiac manifestation of MD1 may be LVHT which alone has no therapeutic implication.

背景与目标： 背景：以前在I型强直性肌营养不良症（MD1）中尚未描述左室超束（LVHT）。
病例报告：自1992年以来，一名42岁的男性出现了MD1的典型特征。肌酸激酶轻微升高，但反复升高。针状肌电图是肌源性的，并显示出广泛的自发活动。肌肉活检与MDI兼容。 DNA分析显示，染色体19q13.3上的肌强直性营养不良蛋白激酶基因杂合了300个CTG重复序列。心脏病史和临床心脏检查均正常。在ECG上，发现ST抬高和房扑。除心房扑动外，AECG正常。出乎意料的是，经胸超声心动图显示LVHT，以前仅在贝克尔的肌营养不良症，线粒体病和Barth综合征中有所描述。
结论：MDHT的一种罕见的心脏表现可能是LVHT，仅LVHT就没有治疗意义。

BACKGROUND & AIMS: :In addition to the priority in the discovery of the first water channel protein in the red blood cell membrane the group of Gheorghe Benga in Cluj-Napoca, Romania, also has a world priority in the discovery of the implications of water channel proteins in epilepsy and Duchenne muscular dystrophy. This priority is briefly presented here. In 1977 Benga and Morariu reported a decreased water permeability of red blood cells in children with idiopathic epilepsy (cases selected by Ileana Benga). This investigation was performed as part of a program of research of hydroelectrolytic alterations in child epilepsy. On the other hand the group of Gheorghe Benga has reported a decreased water permeability of RBC in patients with Duchenne muscular dystrophy. These findings were interpreted as an expression of generalized membrane defects affecting water permeability in epilepsy and Duchenne muscular dystrophy. In recent years this idea was confirmed by reports indicating aquaporin abnormalities in the brain of epileptic patients and in the muscle of Duchenne muscular dystrophy patients.

背景与目标： ：除了优先发现红细胞膜中的第一个水通道蛋白外，罗马尼亚克卢日-纳波卡的Gheorghe Benga小组在发现水通道蛋白在癫痫中的意义方面也具有世界优先地位和杜氏肌营养不良症。在此简要介绍此优先级。 1977年，Benga和Morariu报告了特发性癫痫患儿（Ileana Benga选择的病例）中红细胞的透水性降低。这项研究是儿童癫痫中水电解改变研究计划的一部分。另一方面，Gheorghe Benga小组报告了Duchenne肌营养不良患者的RBC透水性降低。这些发现被解释为影响癫痫和杜氏肌营养不良症中透水性的广义膜缺损的表达。近年来，有报道表明癫痫患者的大脑和杜兴氏肌营养不良患者的肌肉中存在水通道蛋白异常，这一观点得到了证实。

BACKGROUND & AIMS: :Folate and vitamin B12 are essential cofactors for the methionine/homocysteine cycle in the brain. These vitamins mediate the remethylation of homocysteine (HCY), which affects the production of the universal methyl donor, S-adenosylmethionine (SAM), in the brain among other organs. Acquired or inherited disorders in these metabolic pathways are associated with brain abnormalities and severe neurological symptoms that are mostly irreversible, even after providing the missing cofactors. This review discusses the relationship between brain and blood levels of key vitamins and metabolites related to one carbon metabolism.

背景与目标： ：叶酸和维生素B12是大脑中蛋氨酸/高半胱氨酸循环的重要辅助因子。这些维生素介导高半胱氨酸（HCY）的再甲基化，这会影响大脑其他器官中通用甲基供体S-腺苷甲硫氨酸（SAM）的产生。这些代谢途径中的获得性或遗传性疾病与脑部异常和严重的神经系统症状有关，即使提供了缺失的辅因子后，这些症状通常也是不可逆的。这篇评论讨论了大脑和血液中与一种碳代谢有关的关键维生素和代谢物的水平之间的关系。

BACKGROUND & AIMS: :Heart failure patients are clinically characterized by extreme cardiomegaly, breathlessness, fluid retention and an early onset of fatigue. Studies have shown generalized restricted blood flow in those patients. Furthermore animal experiments proved an impaired blood flow and a diminished oxygen supply of the skeletal muscle in animals with chronic heart failure. Patients with chronic heart failure are limited to the extent of their ability to regulate their arterial pressure, especially in physical activity. It is however unclear in what way restriction of blood flow in the main arteries correlates with those in capillaries and to what extent. In this study it was examined the depth of capillary circulatory restriction as well as the disregulation of oxygen partial pressure in skeletal muscle in rest and stress conditions, in patients with terminal heart failure.

背景与目标： 心力衰竭患者的临床特征是极端的心脏肥大，呼吸困难，体液retention留和疲劳的早期发作。研究表明，这些患者的血流普遍受限。此外，动物实验证明，患有慢性心力衰竭的动物的血流量受损，骨骼肌的氧气供应减少。患有慢性心力衰竭的患者被限制在调节其动脉压的能力范围内，特别是在体育锻炼中。然而，尚不清楚主要动脉中的血流限制与毛细血管中的血流以何种方式相关以及在何种程度上相关。在这项研究中，检查了患有终末心力衰竭的患者中毛细血管循环限制的深度，以及在休息和压力条件下骨骼肌中氧分压的失调。

BACKGROUND & AIMS: :Spinal muscular atrophy (SMA) is a hereditary neurodegenerative disease with severity ranging from progressive infantile paralysis and premature death (type I) to limited motor neuron loss and normal life expectancy (type IV). Without disease-modifying therapies, the impact is profound for patients and their families. Improved understanding of the molecular basis of SMA, disease pathogenesis, natural history, and recognition of the impact of standardized care on outcomes has yielded progress toward the development of novel therapeutic strategies and are summarized. Therapeutic strategies in the pipeline are appraised, ranging from SMN1 gene replacement to modulation of SMN2 encoded transcripts, to neuroprotection, to an expanding repertoire of peripheral targets, including muscle. With the advent of preliminary trial data, it can be reasonably anticipated that the SMA treatment landscape will transform significantly. Advancement in presymptomatic diagnosis and screening programs will be critical, with pilot newborn screening studies underway to facilitate preclinical diagnosis. The development of disease-modifying therapies will necessitate monitoring programs to determine the long-term impact, careful evaluation of combined treatments, and further acceleration of improvements in supportive care. In advance of upcoming clinical trial results, we consider the challenges and controversies related to the implementation of novel therapies for all patients and set the scene as the field prepares to enter an era of novel therapies. Ann Neurol 2017;81:355-368.

背景与目标： ：脊髓性肌萎缩症（SMA）是一种遗传性神经退行性疾病，其严重程度从进行性婴儿瘫痪和过早死亡（I型）到有限的运动神经元丧失和正常预期寿命（IV型）不等。如果没有改善疾病的疗法，对患者及其家属的影响将是深远的。对SMA分子基础，疾病发病机制，自然病史以及对标准化治疗对预后的影响的认识得到了更好的理解，这为新型治疗策略的发展带来了进步，并对其进行了总结。评估中的治疗策略包括SMN1基因替换，SMN2编码转录物的调节，神经保护以及包括肌肉在内的周围靶标的扩展库。随着初步试验数据的出现，可以合理地预期SMA治疗前景将发生重大变化。症状前诊断和筛查计划的进展将至关重要，目前正在进行试点新生儿筛查研究以促进临床前诊断。疾病缓解疗法的发展将需要制定监测计划，以确定长期影响，对联合治疗进行认真评估，并进一步加速支持治疗的改善。在即将到来的临床试验结果公布之前，我们考虑了为所有患者实施新疗法带来的挑战和争议，并为该领域准备进入新疗法时代做好了准备。 Ann Neurol 2017; 81：355-368。

BACKGROUND & AIMS: :Myostatin is a negative regulator of skeletal muscle growth. Myostatin mutations and pharmacological strategies increase muscle mass in vivo, suggesting that myostatin blockade may prove useful in diseases characterized by muscle wasting, such as the muscular dystrophies. We subjected the gamma-sarcoglycan-deficient (Sgcg(-/-)) mouse model of limb-girdle muscular dystrophy (LGMD) 2C to antibody-mediated myostatin blockade in vivo. Myostatin inhibition led to increased fiber size, muscle mass, and absolute force. However, no clear improvement in muscle histopathology was evident, demonstrating discordance between physiological and histological improvement. These results and previous studies on the dyw/dyw mouse model of congenital muscular dystrophy and in the late-stage delta-sarcoglycan-deficient (Sgcd(-/-)) mouse model of LGMD2F document disease-specific limitations to therapeutic strategies based on myostatin blockade in the more severe mouse models of different muscular dystrophies.

背景与目标： ：肌生长抑制素是骨骼肌生长的负调节剂。肌肉生长抑制素的突变和药理学方法会增加体内肌肉的质量，这表明肌肉生长抑制素的阻断可能在以肌肉萎缩为特征的疾病（如肌肉营养不良）中被证明是有用的。我们经历了肢带肌肉萎缩症（LGMD）2C的γ-肌糖蛋白缺乏（Sgcg（-/-））小鼠模型体内抗体介导的肌生长抑制素阻断作用。抑制肌生长抑制素导致纤维大小，肌肉质量和绝对力增加。但是，肌肉组织病理学没有明显改善，表明生理和组织学改善之间不一致。这些结果和关于先天性肌营养不良的dyw / dyw小鼠模型以及LGMD2F的晚期δ-肌糖缺乏症（Sgcd（-/-））小鼠模型的先前研究记录了基于肌肉生长抑制素的疾病特异性治疗策略的局限性在不同肌肉营养不良的更严重的小鼠模型中具有阻断作用。

BACKGROUND & AIMS: :Mutation of a receptor tyrosine kinase gene, Mertk, in the Royal College of Surgeons (RCS) rat results in defective phagocytosis of photoreceptor outer segments by the retinal pigment epithelium (RPE) and retinal degeneration. We screened the human orthologue, MERTK, located at 2q14.1 (ref. 10), in 328 DNA samples from individuals with various retinal dystrophies and found three mutations in three individuals with retinitis pigmentosa (RP). Our findings are the first conclusive evidence implicating the RPE phagocytosis pathway in human retinal disease.

背景与目标： ：在皇家外科医学院（RCS）大鼠中酪氨酸受体激酶基因Mertk的突变导致视网膜色素上皮（RPE）和视网膜变性导致光感受器外部节段的吞噬功能缺陷。我们在来自患有各种视网膜营养不良的个体的328个DNA样本中筛选了位于2q14.1（参考文献10）的人类直向同源基因MERTK，并在三个患有色素性视网膜炎（RP）的个体中发现了三个突变。我们的发现是人类视网膜疾病中涉及RPE吞噬途径的第一个确凿证据。

BACKGROUND & AIMS: :Myotonic dystrophy type 2 (DM2) is caused by expansion of a tetranucleotide CCTG repeat in intron 1 of the ZNF9 gene on chromosome 3q21. All studied DM2 mutations have been reported in Caucasians and share an identical haplotype, suggesting a common founder. We identified a Japanese patient with DM2 and showed that the affected haplotype is distinct from the previously identified DM2 haplotype shared among Caucasians. These data strongly suggest that DM2 expansion mutations originate from separate founders in Europe and Japan and are more widely distributed than previously recognized.

背景与目标： ：2型肌强直性营养不良（DM2）是由3q21号染色体上ZNF9基因内含子1中四核苷酸CCTG重复序列的扩增引起的。所有已研究的DM2突变均已在高加索人中报道，并具有相同的单倍型，表明是一个共同的创始人。我们确定了一名患有DM2的日本患者，并表明受影响的单倍型与之前在高加索人中共享的DM2单倍型不同。这些数据有力地表明，DM2扩展突变来自欧洲和日本的不同创始人，并且比以前公认的分布更广泛。

BACKGROUND & AIMS: :Anesthesia for patients with Steinert's syndrome (myotonic dystrophy, MD) is a challenge for the anaesthetist. MD is a multisystemic disease and the neuromuscular symptoms can be associated with sleep apnea, endocrine disorders (diabetes, hypogonadism, hypothyroidism), cardiac, gastroenteric or cognitive disorders (mental deficiency, attention disorders). The diagnosis is facilitated when one or more of these symptoms are associated with the neuromuscular symptoms; however, the latter are not always present at the onset, which makes the diagnosis of MD a difficult and often late one. The choice of drugs and the choice of anesthesia in these patients can be very challenging for many reasons. A myotonic crisis can be triggered by several factors including hypothermia, shivering and mechanical or electrical stimulation. These patients are very sensitive to the usual anesthetics such as hypnotics and paralyzing agents (both depolarizing and nondepolarizing). The following case report describes pathophysiological considerations and a technique for anaesthesia during thoracic surgery that has been able to assure hemodynamic peroperative stability, early extubation and prolonged respiratory autonomy in a patient affected by this genetic disorder.

背景与目标： Steinert综合征（强直性营养不良，MD）患者的麻醉对于麻醉师而言是一项挑战。 MD是一种多系统疾病，其神经肌肉症状可能与睡眠呼吸暂停，内分泌失调（糖尿病，性腺功能减退，甲状腺功能减退），心脏，胃肠道或认知障碍（精神缺陷，注意障碍）有关。当这些症状中的一种或多种与神经肌肉症状相关时，有助于诊断。然而，后者并不总是在发病时就出现，这使得MD的诊断非常困难，而且常常是晚期。由于许多原因，这些患者的药物选择和麻醉选择可能非常具有挑战性。强直性危机可由多种因素触发，包括体温过低，发抖以及机械或电刺激。这些患者对常规麻醉剂（例如催眠药和麻痹剂（去极化和非去极化））非常敏感。以下病例报告描述了在胸外科手术期间麻醉的病理生理学考虑和一种技术，该技术已能够确保受这种遗传病影响的患者的血流动力学稳定性，早期拔管和延长的呼吸自主性。

BACKGROUND & AIMS: :Neuromuscular disorders encompass a heterogeneous group of conditions that impair the function of muscles, motor neurons, peripheral nerves, and neuromuscular junctions. Being the most common and most severe type of muscular dystrophy, Duchenne muscular dystrophy (DMD), is caused by mutations in the X-linked dystrophin gene. Loss of dystrophin protein leads to recurrent myofiber damage, chronic inflammation, progressive fibrosis, and dysfunction of muscle stem cells. Over the last few years, there has been considerable development of diagnosis and therapeutics for DMD, but current treatments do not cure the disease. Here, we review the current status of DMD pathogenesis and therapy, focusing on mutational spectrum, diagnosis tools, clinical trials, and therapeutic approaches including dystrophin restoration, gene therapy, and myogenic cell transplantation. Furthermore, we present the clinical potential of advanced strategies combining gene editing, cell-based therapy with tissue engineering for the treatment of muscular dystrophy.

背景与目标： 神经肌肉疾病包括一组异类疾病，这些疾病会损害肌肉，运动神经元，周围神经和神经肌肉接头的功能。杜兴氏肌营养不良症（DMD）是最常见，最严重的肌营养不良症，是由X连锁肌营养不良蛋白基因的突变引起的。肌营养不良蛋白的丢失会导致肌纤维复发，慢性炎症，进行性纤维化和肌肉干细胞功能障碍。在过去的几年中，DMD的诊断和治疗方法有了长足的发展，但是目前的治疗方法不能治愈该疾病。在这里，我们将回顾DMD发病机理和治疗方法的当前状态，重点关注突变谱，诊断工具，临床试验以及包括肌营养不良蛋白修复，基因治疗和成肌细胞移植在内的治疗方法。此外，我们介绍了结合基因编辑，基于细胞的治疗与组织工程技术治疗肌肉营养不良的先进策略的临床潜力。

BACKGROUND & AIMS: OBJECTIVE:The aim of this study was to assess sensitivity and specificity of surrogate physical ability tests as predictors of criterion firefighting task performance and to identify corresponding minimum muscular strength and endurance standards. METHODS:Fifty-one (26 male; 25 female) participants completed three criterion tasks (ladder lift, ladder lower, ladder extension) and three corresponding surrogate tests [one-repetition maximum (1RM) seated shoulder press; 1RM seated rope pull-down; repeated 28 kg seated rope pull-down]. Surrogate test standards were calculated that best identified individuals who passed (sensitivity; true positives) and failed (specificity; true negatives) criterion tasks. RESULTS:Best sensitivity/specificity achieved were 1.00/1.00 for a 35 kg seated shoulder press, 0.79/0.92 for a 60 kg rope pull-down, and 0.83/0.93 for 23 repetitions of the 28 kg rope pull-down. CONCLUSIONS:These standards represent performance on surrogate tests commensurate with minimum acceptable performance of essential strength-based occupational tasks in UK firefighters.

背景与目标： 目的：本研究的目的是评估替代体力测试的敏感性和特异性，以作为标准消防任务表现的预测指标，并确定相应的最低肌力和耐力标准。
方法：51名（男26名；女25名）参与者完成了三个标准任务（梯子抬高，梯子下降，梯子伸展）和三个相应的替代测试[最大重复坐姿（1RM），肩部推举； 1RM落座式绳索下拉；重复28 kg坐下的绳索下拉]。计算替代测试标准可以最好地识别通过（敏感性；真阳性）和失败（特异性；真阴性）标准任务的人员。
结果：最佳的灵敏度/特异度是：35 kg的肩部推举时为1.00 / 1.00，60 kg的拉绳器为0.79 / 0.92，23次重复28 kg的拉绳器为0.83 / 0.93。
结论：这些标准代表在替代测试中的性能，与在英国消防员中基于强度的基本职业任务的最低可接受性能相当。

BACKGROUND & AIMS: BACKGROUND:Duchenne muscular dystrophy (DMD) is an X-linked recessive disease that affects 1 in 3500-6000 male births. Despite broad research aiming to improve muscle function as well as heart and brain function, sufficient therapeutic efficacy has not yet been achieved and current therapeutic management is still supportive. In a recent pilot trial, oral treatment with L-arginine and metformin showed consistent changes of muscular metabolism both in vitro and in vivo by raising NO levels and expression of mitochondrial proteins in the skeletal muscle tissue of patients with DMD. This randomised, double-blind, placebo-controlled trial aims to demonstrate the superiority of L-citrulline and metformin therapy over placebo in DMD patients with regard to the Motor Function Measure (MFM) D1 subscore (primary endpoint) as well as additional clinical and subclinical tests. METHODS/DESIGN:A total of 40-50 ambulant patients with DMD will be recruited at the outpatient department of the University of Basel Children's Hospital (Switzerland), as well as from the DMD patient registries of Switzerland, Germany and Austria. Patients will be randomly allocated to one of the two arms of the study and will receive either a combination of L-citrulline and metformin or placebo for 26 weeks. Co-medication with glucocorticoids is allowed. The primary endpoint is the change of the MFM D1 subscore from baseline to week 26 under L-citrulline and metformin therapy. Secondary endpoints will include the motor function measure (MFM) and its items and subscores, the 6-minute walking test, timed function tests and quantitative muscle testing. Furthermore, quantitative muscle MRI assessment to evaluate the muscle fat fraction as well as safety and biomarker laboratory analyses from blood will be included. For comparison, muscle metabolism and mitochondrial function will be analysed in 10-20 healthy age-matched male children. DISCUSSION:The aim of this study is to test if a 6-month treatment of a combination of L-citrulline and metformin is more effective than placebo in preventing loss of motor function and muscle degeneration in DMD. The MFM D1 subscore is used as a clinical outcome measure and a quantitative muscle MRI assessment as the surrogate outcome measure of fatty muscle degeneration. TRIAL REGISTRATION:ClinicalTrials.gov: NCT01995032 . Registered on 20 November 2013.

背景与目标： 背景：杜氏肌营养不良症（DMD）是一种X连锁隐性疾病，影响3500-6000名男性出生中的1名。尽管有旨在改善肌肉功能以及心脏和脑功能的广泛研究，但尚未获得足够的治疗效果，并且目前的治疗管理仍是支持性的。在最近的一项先导试验中，口服L-精氨酸和二甲双胍治疗通过提高DMD患者骨骼肌组织中的NO水平和线粒体蛋白的表达，显示出体内和体外肌肉代谢的持续变化。这项随机，双盲，安慰剂对照试验旨在证明在运动功能量度（MFM）D1子评分（主要终点）以及其他临床和研究方面，DMD患者中L-瓜氨酸和二甲双胍治疗优于安慰剂。亚临床测试。
方法/设计：将在瑞士巴塞尔儿童医院大学的门诊部以及瑞士，德国和奥地利的DMD患者登记处招募40-50名DMD流动患者。患者将被随机分配至研究的两个部门之一，并将接受L-瓜氨酸和二甲双胍的组合或安慰剂治疗26周。允许与糖皮质激素合用。主要终点是在L-瓜氨酸和二甲双胍治疗下MFM D1子评分从基线到第26周的变化。次要终点包括运动功能量度（MFM）及其项目和分项，6分钟步行测试，定时功能测试和定量肌肉测试。此外，将包括定量肌肉MRI评估以评估肌肉脂肪含量以及血液中的安全性和生物标志物实验室分析。为了进行比较，将对10至20名年龄匹配的健康男孩进行肌肉代谢和线粒体功能分析。
讨论：这项研究的目的是检验L-瓜氨酸和二甲双胍联合治疗6个月是否比安慰剂更有效，以防止DMD的运动功能丧失和肌肉变性。 MFM D1子评分被用作临床结果测量指标，定量肌肉MRI评估被用作脂肪肌肉变性的替代结果指标。
试验注册：ClinicalTrials.gov：NCT01995032。 2013年11月20日注册。

BACKGROUND & AIMS: :Pain is a frequent problem following recent traumatic spinal cord injury (SCI). Of specific concern in the rehabilitation setting is function-limiting hand pain which prevents optimal participation in therapy and limits independence. A treatable etiology of function-limiting hand pain in SCI is the reflex sympathetic dystrophy syndrome (RSDS). The presentation of RSDS in patients with recent SCI can be easily confused with that of dysesthetic (central origin) or radicular pain. Previous reports of RSDS associated with recent traumatic SCI have not been based on specific clinical criteria outlined in recent literature, and treatment has not been evaluated by objective outcome measures. This report describes 5 cases of RSDS associated with recent traumatic SCI that are identified by specific clinical criteria and are confirmed by a 3 phase bone scan. It is suggested that aggressive early intervention is necessary to obtain optimal functional outcome and minimize length of hospital-based rehabilitation.

背景与目标： ：疼痛是最近的创伤性脊髓损伤（SCI）之后的常见问题。在康复环境中，特别需要关注的是功能受限的手部疼痛，这会妨碍最佳地参与治疗并限制独立性。 SCI中一种限制功能性手痛的可治疗病因是反射性交感神经营养不良综合征（RSDS）。患有新近SCI的患者的RSDS表现很容易与感觉异常（中心性起源）或神经根性疼痛相混淆。先前与近期创伤性SCI相关的RSDS的报道尚未基于近期文献中概述的特定临床标准，并且尚未通过客观的结局指标评估治疗方法。该报告描述了5例与最近的创伤性SCI相关的RSDS病例，这些病例通过特定的临床标准进行了鉴定，并通过3期骨扫描得以证实。建议积极的早期干预对于获得最佳的功能预后并最大程度地减少医院康复的时间是必要的。

BACKGROUND & AIMS: :Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by mutations in the dystrophin gene. We studied 106 patients with a diagnosis of probable DMD/BMD by analyzing 20 exons of the dystrophin gene in their blood and, in some of the cases, by immunohistochemical assays for dystrophin in muscle biopsies. In 71.7% of the patients, deletions were found in at least one of the exons; 68% of these deletions were in the hot-spot 3' region. Deletions were found in 81.5% of the DMD cases and in all the BMD cases. The cases without deletions, which included the only woman in the study with DMD, had dystrophin deficiency. The symptomatic female carriers had no deletions but had abnormal dystrophin distribution in the sarcolemma (discontinuous immunostains). The following diagnoses were made for the remaining cases without deletions with the aid of a muscle biopsy: spinal muscular atrophy, congenital myopathy; sarcoglycan deficiency and unclassified limb-girdle muscular dystrophy. Dystrophin analysis by immunohistochemistry continues to be the most specific method for diagnosis of DMD/BMD and should be used when no exon deletions are found in the dystrophin gene in the blood.

背景与目标： ：Duchenne肌营养不良症（DMD）和Becker肌营养不良症（BMD）由肌营养不良蛋白基因的突变引起。我们通过分析血液中的肌营养不良蛋白基因的20个外显子，对某些诊断为DMD / BMD的患者进行了研究，在某些情况下，还通过免疫组织化学方法对肌肉活检中的肌营养不良蛋白进行了分析。在71.7％的患者中，至少有一个外显子被发现缺失。这些缺失中的68％位于热点3'区域。在81.5％的DMD病例和所有BMD病例中均发现缺失。没有删除的病例，包括研究中仅有的一名患有DMD的女性，患有肌营养不良蛋白缺乏症。有症状的女性携带者没有缺失，但肌膜中的肌营养不良蛋白分布异常（不连续的免疫染色）。余下的病例在肌肉活检的帮助下对没有缺失的病例做出了以下诊断：脊髓性肌萎缩，先天性肌病；肌糖蛋白缺乏和未分类的肢带型肌营养不良症。通过免疫组织化学进行肌营养不良蛋白分析仍然是诊断DMD / BMD的最具体方法，当血液中肌营养不良蛋白基因中未发现外显子缺失时，应使用肌营养不良蛋白分析。