muscular dystrophy
“Dys”的意思是不良的，“troph”的意思是营养；所以肌营养不良主要是肌肉由于退化，表现为营养不良，同时导致肌无力——
在显微镜下，活检组织显示了肌肉本质的改变，而非神经或神经肌肉接头；区别于其他由于神经损伤造成肌无力的因素，如神经损伤疾病neuropathies。
With muscular dystrophy,“dys”means bad or difficult, and“troph”means nourish; so muscular dystrophy basically refers to the muscle appearingpoorly nourished because of degeneration, which leads to muscle weakness.
Under a microscope, a biopsy of the tissue shows changes in the muscle itself but not in the nerve or neuromuscular junction; this distinguishes muscular dystrophy from other problems that cause muscle weakness as a result of nerve damage, like neuropathies.
杜兴与贝克型肌营养不良
肌营养不良是一系列由基因突变导致的功能紊乱。这些功能紊乱中，抗肌萎缩蛋白病dystrophinopathies 是最常见的，包括杜兴肌营养不良（DMD）和贝克尔肌营养不良（BMD）。二者都是有抗肌萎缩蛋白基因突变导致的。
Muscular dystrophy is actually a group of disorders, all of which are caused by genetic mutations. Within that group, dystrophinopathies are the most common, which includes Duchenne muscular dystrophy, or DMD, and Becker muscular dystrophy, both of which result from mutations in the dystrophin gene.
此外，其它基因的突变导致了其它几十种肌营养不良，其中一些基因编码形成抗肌萎缩蛋白相关蛋白复合体的蛋白质，因此这些肌营养不良症，会呈现出与抗肌萎缩蛋白病dystrophinopathies 相同的症状。
In addition to those two, genetic mutations in other genes are responsible for several dozen other muscular dystrophies, some of which code for proteins that form a protein complex with dystrophin protein. These other muscular dystrophies, therefore end up causing a lot of the same symptoms as the dystrophinopathies.
DMD和BMD都是由于同一抗肌萎缩蛋白基因突变引起的，意味着二者是“等位基因疾病allelic disorders”。当突变（如无义突变或移码突变a nonsense or a frameshift mutation）使得抗肌萎缩蛋白严重缺乏时，导致DMD，症状通常于5岁出现，该疾病的结局比BMD更严重。另一方面，突变（如错义突变missense mutations）若产生畸形蛋白，会导致BMD，病情比DMD较轻，发病年龄较晚，一般在10到20岁。Now, the fact that both Duchenne and Becker muscular dystrophy result from mutations in the same dystrophin gene means that they are“allelic disorders”, and when a mutation occurs in dystrophin that’s severe enough to result in no protein at all, for example a nonsense or a frameshift mutation, the result is Duchenne muscular dystrophy, which ends up being the more severe of the two, with symptoms usually presenting by age 5.
On the other hand, mutations that allow for a misshapen protein to form, like missense mutations, lead to Becker muscular dystrophy which is basically a milder form of Duchenne muscular dystrophy that presents later on, usually between age 10 to 20.
抗肌萎缩蛋白基因
抗肌萎缩蛋白基因是X染色体上一个庞大的基因，含有79个外显子exons，全长超过2000kbp（书上通常缩写为bp，碱基对）；相形之下，大多数基因只有10个外显子和50kbp长。更多的碱基对和外显子意味着减数分裂meiosis 时有更多出错的可能，会形成X染色体上有错误编码序列的卵子或精子。基因突变大多数为一个或多个外显子的缺失或重复，小部分是点突变point mutation。
Alright so the dystrophin gene is a huge gene on the X-chromosome, that has 79 exons and is over 2 million base pairs in length. By comparison, most genes have only about 10 exons and are 50 thousand base pairs in length.
More base pairs and more exons mean that there are more chances for mistakes during meiosis, which is when the egg or sperm are being created. Most of these gene mutations are deletions or duplications of one or more exons, and a small amount are point mutations.
男性有一个X染色体和一个Y染色体，女性有两个X染色体；这意味着该病常见于男性，因为他们只有一套抗肌萎缩蛋白基因模板，如果该模板有错误，肌纤维也没有其它选择了。然而女性就算有一个有缺陷的基因，可能另一个是功能正常的。由于发病与X染色体有关联，DMD和BMD被称为X连锁隐性遗传X-linked recessive。
Now males males have one X and one Y chromosome, and females have two X chromosomes. This means it’s way more common in boys, because they only have one copy of the dystrophin gene, and if that copy’s defective, it’s the only one available to muscle cells, whereas girls with a defective dystrophin gene might have another functional one. Since this is linked to the X chromosome, both Duchenne and Becker muscular dystrophy are called X-linked recessive.
女性只有一条X染色体表达，而另一条失活，这就是X染色体失活（莱昂化lyonization）。如果失活是随机的，可以预料到女性一半的细胞中抗肌萎缩蛋白基因是有功能的，另一半是有缺陷的，通常这些人无临床症状。机体中如果更多细胞有该基因缺陷，剩下更少的功能正常基因的就更少，这一类人群就是“显性携带者manifesting carriers”，他们会有部分症状表现。
In females, though, only one X chromosome gets expressed, and the other is inactivated, called X-inactivation or lyonization. Now if this inactivation’s random, you’d expect about half of the female’s cells to have a functional dystrophin gene and the other half to have a defective dystrophin gene, and these people are typically asymptomatic. Having said that, if more cells end up with the defective dystrophin gene, and less with the functional one, they can end up being“manifesting carriers”, meaning that they manifest or show some symptoms.
抗肌萎缩蛋白
抗肌萎缩蛋白，通过抗肌萎缩蛋白相关蛋白复合体，与细胞内肌动蛋白actin 连接。这个蛋白复合体是一连串胞质胞膜蛋白，与肌纤维周围的细胞外基质锚定，以连接细胞骨架肌动蛋白与细胞外基质，稳定肌膜sarcolemma，就像一根沿着屋顶的木制承重横梁，维持着房子的稳定。
Alright so the dystrophin protein links intracellular actin with the“dystrophin-associated protein complex”, which is a cluster of cytoplasmic and cell membrane proteins that are anchored to the extracellular matrix around the muscle cell, making that link between cytoskeletal actin and the extracellular matrix stabilizesthe sarcolemma, or muscle cell membrane, in the same way that a large wooden support beam running along the roof keeps a house sturdy.
没有抗肌萎缩蛋白的支撑，肌膜萎塌wilt，变得不稳定。时间一长，细胞蛋白（肌酸激酶creatine kinase, CK）溢出损伤的细胞，钙离子进入细胞，最终造成细胞死亡。短期内，肌肉可再生，造成肌纤维尺寸参差不齐；长此以往，肌肉萎缩并且脂肪组织和结缔纤维组织增生渗入其间，导致肌肉无力。
Without the support of dystrophin in place, the sarcolemma essentially wilts and becomes unstable. Over time, cellular proteins like creatine kinase, or CK, start escaping the damaged cell and calcium starts to enter the cell, and this ultimately leads to cell death.
In the short term, there is muscle regeneration resulting in muscle fibers of different sizes, but in the long term, the muscles atrophy and are infiltrated by fat and fibrotic tissue, which leaves them really weak.
症 状
上述过程以腿部症状最为明显，DMD患儿在童年时期学步晚，表现为“鸭步waddling gait”，他们小腿肚表现为假性肥大，但小腿肌视觉上的增大并不是由于肌肉组织，而是脂肪组织和纤维组织。
This process is particularly noticeable in the legs, and children with Duchenne muscular dystrophy begin to walk later in childhood, and they have they have a“waddling”gait, and they tend to develop calf pseudohypertrophy, where they have visibly enlarged calves which are large because of fat and fibrotic tissue rather than muscle tissue.
DMD另一典型体征是Gower征，小儿腹部朝下平躺状态下，他们需要借助双臂让自己缓慢站起，这是因为臀部和大腿周围的肌肉无力。
Another classic sign of Duchenne muscular dystrophy is Gowers’sign, where if a child is lying down flat on their stomach, they will slowly stand up with the help of their arms, because of weak muscles around the hips and upper legs.
后期症状包括，由于严重的肌无力需坐轮椅，由于膈肌无力会发生呼吸衰竭，脊柱侧凸scoliosis，扩张性心肌病dilated cardiomyopathy 和心律失常arrhythmia，因为抗肌萎缩蛋白也表达于心肌纤维；很不幸，这些并发症通常会缩短寿命。
Later symptoms include needing a wheelchair because of severe weakness, developing respiratory failure because of a weak diaphragm, scoliosis, and developing dilated cardiomyopathy and arrhythmias since the dystrophin protein is also expressed in heart muscle. Unfortunately, these complications often lead to a shortened lifespan.
诊 疗 诊断DMD或BMD一般有肌酸激酶creatine kinase level 升高，确诊需要找到抗肌萎缩蛋白基因的突变（通过DNA测试或蛋白质免疫印迹Western blot）以及肌肉活检（抗肌萎缩蛋白染色）。
For diagnosis, people with Duchenne or Becker muscular dystrophy often have a high creatine kinase level, and the diagnosis can be confirmed by looking for mutations in dystrophin （by either DNA tests or Western blot）, as well as having a muscle biopsy with staining for dystrophin.
不幸的是，DMD或BMD暂时没有好的治疗方法：糖皮质激素glucocorticoids 有时可以减慢进程，但是有副作用，如肥胖。物理治疗和训练可以提高生活质量，但是无法从本质逆转进程。
Unfortunately, there are no great treatments for Duchenne or Becker muscular dystrophy. Glucocorticoids can sometimes slow degeneration, but can also result in side effects like excessive weight gain. Other treatments like physical therapy and conditioning can improve quality of life, but they don’t reverse the underlying process.
考虑到遗传的可能性，询问患者父母很重要，使其了解生育另一个患儿的风险。母亲为携带者的情况，约占三分之二；另外三分之一为散发sporadic，是新的突变导致。如果母亲是携带者，那么她未来的儿子将有50%可能有突变，而诞生的女儿中将有50%可能携带突变基因。
Given the possibility of genetic inheritance, counseling parents of the person and understanding the risk of having another child with these conditions is important. About 2/3 of the time the person’s mother is a carrier and the the other 1/3 of the time the disease is sporadic, which means it’s caused by a new mutation. If the mother is a carrier, and we look at her future sons, half or 50% will end up having the mutation, and if we look at her future daughters, half or 50% of them will be carriers for the mutation.
小 结
抗肌萎缩蛋白对肌纤定性的维持极其重要。基因突变导致的抗肌萎缩蛋白丢失，引起DMD；而突变导致的畸形蛋白，将会引起BMD。
Okay so as a quick recap: the protein dystrophin is super important for stabilizing the muscle cell membrane. Mutations in the dystrophin gene that lead to a loss of dystrophin leads to duchenne muscular dystrophy, whereas mutations in the dystrophin gene that leads to misshapen dystrophin leads to Becker muscular dystrophy.
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