Carrier detection of Duchenne and Becker muscular dystrophy using muscle dystrophin immunohistochemistry.

To ascertain whether dystrophin immunohistochemistry could improve DMD/BMD carrier detection, we analyzed 14 muscle biopsies from 13 DMD and one BMD probable and possible carriers. All women were also evaluated using conventional methods, including genetic analysis, clinical and neurological evaluation, serum CK levels, EMG, and muscle biopsy. In 6 cases, there was a mosaic of dystrophin-positive and dystrophin-deficient fibers that allowed to make the diagnosis of a carrier state. Comparing dystrophin immunohistochemistry to the traditional methods, it was noted that this method is less sensitive than serum CK measurements, but is more sensitive than EMG and muscle biopsy. The use of dystrophin immunohistochemistry in addition to CK, EMG and muscle biopsy. improved the accuracy of carrier detection. This method is also helpful to distinguish manifesting DMD carriers from patients with other neuromuscular diseases like limb-girdle muscular dystrophy and spinal muscular atrophy.     

Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD), an X-linked disorder, is the most common muscular dystrophy in children, presenting in early childhood and characterized by proximal muscle weakness and calf hypertrophy in affected boys. Patients usually become wheelchair-bound by the age of 12 years, and die of cardiorespiratory complications in their late teens to early twenties. Advances in the management of DMD, including treatment with corticosteroids and the use of intermittent positive pressure ventilation have provided improvements in function, ambulation, quality of life and life expectancy, although novel therapies still aim to provide a cure for this devastating disorder. The clinical features, investigations, and management of DMD are reviewed, as well as the latest in some of the novel therapies.     

Carrier detection in severe (type III) von Willebrand disease using two intragenic restriction fragment length polymorphisms

DNA from a family with a female member affected with severe (type III) vWD was analysed using three restriction enzymes and a partial vWF cDNA probe. Two restriction fragment length polymorphisms (RFLPs) detected with the enzymes Bgl II and Xba I proved to be informative in this family. A 36.0 Kb allele demonstrated with the enzyme Xba I was rare in the general population but very important in this family for segregation analysis of the alleles and their association with the putative defective chromosome. The propositus was homozygous for the 36.0 Kb Xba I polymorphic band and heterozygous for the Bgl II polymorphism. She was the only member of the family showing this allelic pattern. The linkage of the alleles could be determined because her mother was homozygous for the 9.0 Kb Bgl II polymorphism but heterozygous for the Xba I polymorphism. The segregation of the alleles could be traced to the proband's son and a niece. The genotypic analysis revealed that her niece could be considered as carrying a defective gene for severe vWD.     

Carrier detection and gene analysis in a Duchenne muscular dystrophy family

Probe C7, pERT87-15, 754 which on the short arm of the X chromosome are used in the linkage analysis of a DMD family by the use of restriction fragment length porlymorphism (RFLP) and serum CPK, CPK-MB are detected. Three obligated carriers are determined and we also find a deletion to pERT87-15 in this family.     

Duchenne muscular dystrophy and epilepsy

Cognitive and behavioral difficulties occur in approximately a third of patients with Duchenne muscular dystrophy. The aim of our study was to assess the prevalence of epilepsy in a cohort of 222 DMD patients. Epileptic seizures were found in 14 of the 222 DMD patients (6.3%). The age of onset ranged from 3 months to 16 years (mean 7.8). Seizures were more often focal epilepsy (n = 6), generalized tonic–clonic seizures (n = 4) or absences (n = 4). They were present in 12 of the 149 boys with normal IQ (8.1%) and in two of the 73 with mental retardation (2.7%). In two cases the parents did not report any past or present history of seizures but only ‘staring episodes’ interpreted as a sign of ‘poor attention’. In both patients EEG showed the typical pattern observed in childhood absence epilepsy. Our results suggest that the prevalence of epilepsy in our study (6.3%) is higher than in the general pediatric population (0.5–1%). The risk of epilepsy does not appear to increase in patients with mental retardation.     

Therapeutics in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a fatal disorder affecting approximately 1 in 3500 live born males, characterized by progressive muscle weakness. Several different strategies are being investigated in developing a cure for this disorder. Until a cure is found, therapeutic and supportive care is essential in preventing complications and improving the afflicted child’s quality of life. Currently, corticosteroids are the only class of drug that has been extensively studied in this condition, with controversy existing over the use of these drugs, especially in light of the multiple side effects that may occur. The use of nutritional supplements has expanded in recent years as researchers improve our abilities to use gene and stem cell therapies, which will hopefully lead to a cure soon. This article discusses the importance of therapeutic interventions in children with DMD, the current debate over the use of corticosteroids to treat this disease, the growing use of natural supplements as a new means of treating these boys and provides an update on the current state of gene and stem cell therapies.     

Duchenne muscular dystrophy manifesting carriers

Seven unrelated women were manifesting carriers of Duchenne muscular dystrophy. A manifesting carrier of Duchenne muscular dystrophy is defined as a female with a history of Duchenne muscular dystrophy in her pedigree who has symptomatic weakness. All were characterized by slowly progressive weakness that began in the second or third decade of life. Asymmetric weakness was present in only three of the seven patients. Serum creatine kinase values were elevated in all patients and none had an electrocardiogram indicating ventricular hypertrophy. The electromyogram and muscle biopsy specimens were reported as myopathic in all patients studied. In the absence of a male relative with Duchenne muscular dystrophy, clinical distinction from cases of autosomal recessive limb girdle muscular dystrophy may not be possible. The development of new techniques in molecular genetics should allow precise identification of manifesting carriers of Duchenne muscular dystrophy in the near future.     

用短串联重复序列单体连锁分析进行肌营养不良症产前基因诊断

目的对２０个迪谢内／贝克肌营养不良症（ＤＭＤ／ＢＭＤ）家系进行产前基因诊断。方法应用多重聚合酶链反应（ｍＰＣＲ）和短串联重复序列（ＳＴＲ）多态单体连锁分析对２０个ＤＭＤ／ＢＭＤ家系的成员进行产前基因分析。结果１６个家系可提供充足的多态性信息，４个散发型家系不能提供多态性信息。１１例男性胎儿中，３例存在基因缺失，４例非缺失型男性胎儿的单体型与其携带者母亲相同，确定为ＤＭＤ胎儿。９例女性胎儿中５例继承了母亲的单体型，为致病基因携带者。５１例先证者母亲及其他女性血亲为杂合型。结论ＳＴＲ单体连锁分析快速、准确，基因组ＤＮＡ需要量小，可提供的信息量高，适合非缺失型ＤＭＤ／ＢＭＤ家系产前诊断的需要。同时选择ＤＭＤ基因两端和基因内４个位点进行连锁分析，可大大提高诊断的准确率     

Duchenne muscular dystrophy and poliomyelitis

Summary A systematic study of dystrophy-denervation in human muscle showed minimal morphometabolic differences between dystrophic and dystrophic-denervated muscle. The only certain conclusion is that denervation influences the rhythm of evolution of the dystrophy without impressing any of the few characteristics considered at present as peculiar to denervation.This work was supported by a grant-in-aid of the Muscular Dystrophy Associations of America, Inc.     

Dystrophin analysis in the differential diagnosis of autosomal recessive muscular dystrophy of childhood and Duchenne muscular dystrophy

We report 2 patients with childhood autosomal recessive muscular dystrophy. Both patients had slight muscle weakness without enlargement of the calf muscles or involvement of the facial muscles. Their clinical courses are static. Muscle histology revealed characteristic features of muscular dystrophy. Dystrophin was identifiable in the sarcolemma of both patients by immunocytochemical staining with an antidystrophin antibody. At an early age, immunocytochemical analysis with antidystrophin antibody was useful in distinguishing between childhood autosomal recessive and Duchenne muscular dystrophies.     

重视Duchenne型肌营养不良症的康复治疗

康复治疗对改善Duchenne型肌营养不良症患者生活质量、延缓病情进展至关重要,一些国家业已制定了康复治疗指南,我国尚缺乏这方面的指导性研究和意见。为了提高临床医师对该病症康复治疗的认识,现对其病情分期、临床特征,以及康复治疗的一般原则、常用方法和注意事项进行概述,为临床康复治疗提供一些参考。