进行性肌营养不良假性肥大型与线粒体病的对比分析

选择进行性肌营养不良假性肥大型（DMD）和线粒体病各6例，从临床特点、血清酶学、电生理及肌肉病理检查进行对比分析。结果DMD临床表现进行性加重从无力，多在3～4a出现假性肥大；血清酶学检查活性升高；肌电图均显示肌源性损害；1／3病例有心脏受累；肌肉病理示多种肌细胞结构紊乱．线粒体病临床表现肌无力较DMD轻，进展较之缓慢，无局灶体征；血清酶学检查均正常，肌电图3／6显示肌源性损害，1／6显示神经源性损害，2／6表现正常；肌肉病理所见线粒体大小及形态异常。认为上述肌病的诊断需根据临床，并结合病理检查、组织生化检测及基因检查综合诊断分析。     

假肥大型肌营养不良的诊断进展

假肥大型肌营养不良是由于dystrophin基因突变引起的X连锁隐性遗传性疾病,表现为肌束内大量脂肪和结缔组织的堆积,导致高致残、致死率.由于该病迄今无特异性治疗,只能对症治疗和支持治疗,所以准确、全面的检测对假肥大肌营养不良患者及携带者有着重要的意义,有助于产前检测避免此类患儿的出生,也是目前解决这一问题的关键所在.该文就血清酶学、肌电生理学、影像学、肌组织病理活检及基因检测等诊断假肥大型肌营养不良的方法进行综述.     

Y特异重复DNA顺序的临床应用

人类遗传性疾病中,性联遗传占据了很大的比例,常见者如血友病A,发病率为1/5000,假性肥大型进行性肌营养不良症(DMD)为1/3000。但在尚缺乏对遗传性疾病特异疗法情况下,产前诊断显得十分重要,DNA 分子克隆技术应用于产前分析是产前诊断近年来新发展的领域。其中Y 特异重复DNA 顺序作早期性别判断及Y 染色体结构异常研究是开展最早,应用最广泛的DNA 探针之一。     

肢带型肌营养不良2D 型1 例临床与基因型分析

目的提高对肢带型肌营养不良2D型临床及基因型特征的认识。方法回顾分析1例肢带型肌营养不良2D型患儿的临床资料,并复习相关文献。结果男性患儿,5岁7个月起病。有进行性肌无力、腓肠肌肥大、Gower征阳性。磷酸肌酸激酶20 602 U/L;肌电图示肌源性损害;肌肉磁共振示双下肢皮下脂肪层及肌肉内见条片状压脂序列高信号,肌肉层著。MLPA检测DMD基因阴性;全外显子测序示SGCA基因第3外显子c.234-235ACGA纯合突变,该位点未见报道,美国医学遗传学与基因组学学会(ACMG)评级为致病性变异,其父母均为杂合携带。患儿最终诊断为肢带型肌营养不良2D型。结论 SGCA c.234-235ACGA变异可能为肢带型肌营养不良2D型新的致病性突变。肌酶明显升高时,除假肥大型肌营养不良症外,还应注意肢带型肌营养不良2D型。     

进行性肌营养不良的治疗进展

进行性肌营养不良的治疗进展山东潍坊医学院附属医院儿科（２６１０３１）牛余宗，张桂春，周军平综述严布帆审校进行性肌营养不良是一组遗传性肌肉变性疾病，以Ｄｕｃｈｅｎｎｅ型肌营养不良（ＤＭＤ）最常见。现已证明，ＤＭＤ的基因缺陷在Ｘｐ２１．２，由于该基因的突...     

进行性肌营养不良假性肥大型与线粒体的对比分析

选择进行性营养不良假性肥大型（ＤＭＤ）和线粒体病各６例，从临床特点、血清酶学、电生理及肌肉病理检查进行对比分析。结果ＤＭＤ临床表现进行性加重肌无力，多在３－４ａ出现假性肥大；血清酶学检查活性升高；肌电图均显示肌生损害；１／３病例有心脏受累，肌肉病理示多种肌细胞结构紊，线粒体病临床表现肌无力较ＤＭＤ轻，进展较之缓慢，无局灶体征；血清酶学检查均正常；肌电图３／６显示肌源性损害，１／６显示神经源性损害，     

假肥大型肌营养不良基因携带者检测方法的研究进展

假肥大型肌营养不良 (DMD)在儿童神经肌肉系统疾病中发病率高 ,预后差 ,目前尚无有效的治疗方法 ,故携带者的检出对预防患儿出生具有重要意义。传统的检测方法漏诊率高 ,使用有限 ,近年来在基因检测方面取得了一定进展。文章主要介绍假肥大型肌营养不良基因携带者的基因检测方法 ,并将携带者分为缺失型和非缺失型分别进行综述     

骨骼及肌肉系统疾病

551274 进行性肌营养不良假性肥大型血清学的初步研究吴康敏等中华神经精神科杂志18(6):342～345,1985 测定项目有磷酸肌酸激酶(CPK)总活性,乳酸脱氢酶(LDH)、LDH、GOT、GPT总活性及CPK及其同工酶。正常对照组(年龄0～17岁118例),各年龄组男女间无差异,     

良性(Becker型)肌营养不良症

1957年Becker首次提出性连锁遗传肌营养不良症有两种不同类型。一是从幼年起病发展迅速的假性肥大型肌营养不良症,或称Duchenne型肌营养不良症(简称DMD),另一种临床表现相似,但起病较晚、进展缓慢、预后较好的一种新的性连锁遗传肌营养不良症。前者预后极坏,故称之为恶性(或重症)肌营养不良症,后者称之为良性(轻症)肌营养不良症。近来有关良性(Becker型)肌营养不良症的报告不少,已肯定为一种独立的疾病。至于良性肌营养不良症除Becker型     

Duchenne型肌营养不良84例报告

Duchenne型肌营养不良(Duchenne musculardystrophy,DMD),又名假性肥大型肌营养不良,为性连锁隐性遗传中最常见的致死性肌病。女性传递,男性患病,发病率较高,占男婴的1/3500～4800,携带者频率为1/2300,占国内儿科咨询门诊     

疑难病研究：STAT3基因突变致免疫失调综合征

4岁6个月男性患儿,以发热、咳嗽、面色苍白及乏力起病,有肝脾大、淋巴结肿大并全血细胞减少,自幼反复呼吸道及消化道感染,基因检查示STAT3基因存在致病性杂合突变c.C2147 > T （p.T716M）,故该患儿诊断为免疫失调综合征。前期抗感染及不规律激素治疗疗效欠佳,予规律激素治疗后症状好转。该文报道了1例STAT3基因突变致免疫失调综合征,对该病流行病学、临床特征、诊疗等进行归纳总结,为该病的早期诊断、治疗及后续研究提供了参考依据。     

New perspectives in understanding and management of the respiratory disease in cystic fibrosis

In the past 40 years, the mean survival of patients with cystic fibrosis (CF) has increased from less than 1 year to 30 years. The identification of the gene mutated in CF in 1989 has already been followed by the first phase of somatic gene therapy in 1993. The target organ of somatic gene therapy is the respiratory epithelium, which is progressively damaged by the chronic infection and inflammation characteristic of the disease. Since in the future, more patients may benefit from somatic gene therapy, the understanding of the mechanisms leading to chronic infection and inflammation becomes increasingly important. In the future, current therapeutic measures to protect the respiratory epithelium from damage, such as intravenous antimicrobial treatment, will be improved by the additional delivery of new drugs to the bronchial tree by aerosol. Amiloride and recombinant human DNAse administered by this route have the potential to improve mucociliary clearance. Antibiotics as well as protease inhibitors delivered by aerosol should contribute to prevent damage by infection and inflammation in order to increase the probability of successful somatic gene therapy in this disease.     

Gaucher and Fabry diseases: from understanding pathophysiology to rational therapies

Over the past 40 years there has been remarkable development in our understanding of the pathophysiology of lysosomal storage disorders. This review describes the research carried out on the sphingolipid storage disorders from the first demonstration of the underlying metabolic abnormality in Gaucher disease to the development of enzyme replacement therapy for Gaucher and Fabry diseases. Initial developments in gene therapy are also described.
Conclusion : The introduction of enzyme replacement therapy has provided a lifeline for patients with Gaucher or Fabry disease. It is anticipated that future developments, including gene therapy, will provide additional therapeutic options.     

Gaucher and Fabry diseases: from understanding pathophysiology to rational therapies

Over the past 40 years there has been remarkable development in our understanding of the pathophysiology of lysosomal storage disorders. This review describes the research carried out on the sphingolipid storage disorders from the first demonstration of the underlying metabolic abnormality in Gaucher disease to the development of enzyme replacement therapy for Gaucher and Fabry diseases. Initial developments in gene therapy are also described. CONCLUSION: The introduction of enzyme replacement therapy has provided a lifeline for patients with Gaucher or Fabry disease. It is anticipated that future developments, including gene therapy, will provide additional therapeutic options.     

Somatische Gentherapie der Mukoviszidose Aktueller Forschungsstand

Background. Numerous gene mutations associated with hereditary disorders have been identified. In cystic fibrosis the hereditary defect is attributed to mutations in one single gene, the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). Conventional therapies of CF have dramatically increased the life expectancy of afflicted individuals. However, the ultimate incurability of this disease calls for novel and better therapeutic strategies. As cystic fibrosis is believed to be caused by mutations in one single gene, it has appeared to be the ideal candidate for one of the most tempting approaches in clinical therapy, namely gene therapy. Laboratory protocols for the introduction of genes into various tissues have been developed and applied over the last years. The ease of gene transfer under laboratory conditions gave rise to the hope that rapid advances in gene transfer protocols under clinical settings could be achieved as well. Clinical trials. 25 clinical trials of gene therapy for cystic fibrosis have been initiated using viral and non-viral vectors for gene transfer. The outcome of the CF gene therapy studies as well as of those for other diseases have clearly demonstrated that gene transfer and gene therapy in humans is a much more complex and challenging task than originally thought. Still, the encouraging results achieved in animal models and the rapid progress in vector technology justify the hope that the novel genetic therapies will be applied successfully to the benefit of patients suffering from cystic fibrosis.     

Contribution of antineoplastic biotherapy in the treatment of leukemia in children]

Improvements in the chemotherapeutic and transplant regimens have had a significant impact in improving survival rates for pediatric leukemia. However, there are still major problems to address including what options are available for patients with chemoresistant disease and what strategies are available to avoid toxicity associated with highly cytotoxic treatment regimens. Gene and immunotherapy protocols hold great promise. Using gene transfer of a marker gene, a number of biologic issues in the therapy of leukemia have been addressed. For example, by gene marking autologous bone marrow grafts it has been possible to demonstrate that infused marrow contributes to relapse in acute and chronic myeloid leukemias. In the allogeneic transplant setting, genetically modified T-cells have proven valuable for the prophylaxis and treatment of viral diseases and may have an important role in preventing or treating disease relapse. Gene transfer is also being used to modify tumor function, enhance immunogenicity, and confer drug-resistance to normal hematopoietic stem cells. With the continued scientific advancements in this field, gene therapy will almost certainly have a major impact on the treatment of pediatric leukemia in the future.     

Diagnosis and treatment of Wilson's disease

Wilson's disease (WD) has moved on from being a recognized syndrome that was uniformly fatal to a curative disease for which the genetic basis has been discovered. Most pediatric patients present with hepatic manifestations, but some may have neurologic or psychiatric features. Clinical and biochemical screening, including liver biopsy for hepatic copper analysis, remain the standard for diagnosis, but haplotype analysis for siblings is now available and should be considered for family screening when possible. Lifelong medical therapy remains the mainstay of treatment, but treatment preferences are changing from penicillamine to alternative agents such as trientine and zinc. OLT remains lifesaving for those with fulminant WD and those in whom initial medical therapy fails. The future will probably see the application of rapid and accurate molecular diagnostic testing for this disorder and new therapeutic modalities such as hepatocyte transplantation, gene replacement therapy, and gene modification.     

Novel mutation of aspartoacylase gene in a Turkish patient with Canavan disease

Canavan disease is a neurodegenerative disease with autosomal recessive inheritance. Although this disease is prevalant among Ashkenazi Jewish population, several cases have been reported from all over the world. Canavan disease is caused by a genetic mutation in aspartoacylase gene. We have identified a novel mutation, a homozygous C432+1G>A mutation, in a 10-month-old boy who has a typical Canavan phenotype (without macrocephaly) accompanied by typical brain magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and diffusion magnetic resonance findings. The patient's mother was found to be heterozygous for this mutation. We believe that future studies of aspartoacylase gene in various ethnic groups could lead to a better understanding of Canavan's pathophysiology and gene therapy.     

Stem cell and genetic therapies for the fetus

The prenatal diagnosis and management of congenital disease has made significant progress over the previous decade. Currently, fetal therapy (including open surgery and fetoscopic intervention) provides therapeutic options for a range of congenital anomalies; however, it is restricted to the treatment of fetal pathophysiology. Improvements in prenatal screening and the early diagnosis of genetic disease allow for preemptive treatment of anticipated postnatal disease by stem cell or genetic therapy. While currently awaiting clinical application, in utero stem cell therapy has made significant advances in overcoming the engraftment and immunologic barriers in both murine and pre-clinical large animal models. Likewise, proof in principle for fetal gene therapy has been demonstrated in rodent and large animal systems as a method to prevent the onset of inherited genetic disease; however, safety and ethical risks still need to be addressed prior to human application. In this review, we examine the current status and future direction of stem cell and genetic therapy for the fetus.     

Duchenne型肌营养不良基因治疗研究进展

Duchenne型肌营养不良（DMD）是由编码抗肌萎缩蛋白的DMD基因突变导致的X连锁隐性遗传病。它的特点是进行性肌无力和因缺乏抗肌萎缩蛋白而导致的骨骼肌和心肌退化。患儿多于2~5岁起病,常在20岁左右死于心力衰竭或呼吸功能不全。目前,临床上多采用支持疗法改善疾病症状,但并不能改变疾病的最终结局。基因治疗的兴起为该病的治愈提供了希望。本文总结了DMD的基因替代疗法,包括腺相关病毒介导的DMD基因转导技术、肌营养不良蛋白相关蛋白（utrophin）上调技术和成簇规律间隔的短回文重复序列基因编辑技术的研究进展,并为解决腺相关病毒载量、转基因产物的长期有效表达、utrophin蛋白表达量问题提出的建议进行综述,为研究者们进一步研究提供参考。