假肥大型肌营养不良症肌电图表现

目的：总结假肥大型肌营养不良症（DMD）患儿的肌电图特点及其对DMD的诊断价值.方法：对13例DMD患儿的临床特征及病因进行分析,并做神经传导和肌电图（EMG）检测.结果：DMD好发于儿童,以进行性、对称性肌萎缩和肌无力及肢体近端型的特殊分布特点,肌电图呈肌源性改变.结论：肌电图对DMD的临床诊断有重要价值.     

假肥大型肌营养不良症基因诊断及遗传分析

目的对假肥大型肌营养不良症（DMD／BMD）患者进行基因诊断并对家系进行遗传分析,以提高对DMD／BMD的基因诊断水平及有效的遗传咨询。方法对40例DMD／BMD患者应用18对引物多重PCR技术进行Dystrophin基因缺失诊断,收集完整家系资料进行遗传分析以判断致病基因携带者及评估风险。结果40例DMD／BMD患者基因诊断有27例至少存在一个外显子片段缺失（67．5％）,13例未检测到缺失（32．5％）。通过对家系的遗传分析判断出致病基因携带者。结论多重PCR作为一种简便快速的诊断方法可对DMD／BMD患者进行基因诊断;对风险家系进行遗传分析、判断致病基因携带者以进行有效的遗传咨询,进而控制遗传病。     

脐血干细胞移植治疗假肥大型肌营养不良症

目的比较假肥大型肌营养不良症(Duchennemusculardystrophy,DMD)患者经脐血干细胞移植治疗前后其肌肉再生、抗肌萎缩蛋白表达和运动功能的改变;以及评价治疗的安全性。方法对1例经基因分析和肌肉活检及抗肌萎缩蛋白检测确诊的、已丧失行走能力的DMD患儿,经HLA配型,在脐血库中寻找到一个全相合的脐血供体。采用白消安+环磷酰胺+兔抗胸腺淋巴细胞球蛋白预处理后进行异基因脐血干细胞移植;术后采用环孢素A和骁悉方案预防移植物抗宿主反应(graftversushostreaction,GVHD)。同时定期检测原发病的生化指标如血清肌酸激酶(creatinekinase,CK)、造血重建的植入证据(血型转变、肌肉和血液系统的聚合酶链反应短串联重复序列分析)、缺陷基因是否纠正、新生肌肉是否出现、肌肉中抗肌萎缩蛋白是否表达和运动功能是否改善。结果(1)中性粒细胞在脐血干细胞移植后第15天(+15天)达到0.5×109/L,白细胞在+25天达正常水平;血小板于+22天达到20×109/L;血红蛋白维持于85～100g/L。术后140天骨髓穿刺提示三系生长旺盛;(2)移植后140天血型转为供体AB型。至今没有出现移植物抗宿主反应。(3)术后18天、30天、43天、55天、74天、233天患者外周血DNA和术后140天、183天、235天骨髓细胞DNA经PCRSTR检测为供者独立植入;(4)患儿术后60天取外周血做基因分析,显示19号缺失的外显子得到完全纠正,患儿转变为正常基因型;(5)患儿在移植后75天的肌肉活检可见新生肌管形成,抗肌萎缩蛋白免疫组化呈弱阳性,少数为强阳性反应,DNA分析:供者基因DNA占1%～13%;移植后126天抗肌萎缩蛋白免疫组化检测显示阳性的肌纤维明显增多,供者基因DNA上升至2.5%～25%;(6)患儿血清CK从移植治疗前的5735U/L降至274U/L;(7)术后100天体检发现患儿肌力略有改善,肢端温暖。结论异基因脐血干细胞移植治疗DMD,可在移植后短期内重建造血功能、血清CK显著下降、肌肉抗肌萎缩蛋白表达,患儿运动有所改善,提示造血干细胞移植将有益于DMD的治疗。     

良性假肥大型肌营养不良一家系13例

先证者 (Ⅳ8)　男 ,5 2岁。 12岁时自感双下肢无力 ,跑跳落后于同龄人。 2 0岁时病情加重 ,双手抓握无力 ,走路呈“鸭步” ,仰卧时起立困难 ,3 8岁起瘫痪在床。查体 :双上肢肌肉、胸肩肌、腰肌、臀肌群明显萎缩 ,腓肠肌萎缩不明显 (早期肥大 ) ,手指肌腱及下肢肌腱挛缩。心、肺、腹未见明显异常。患者曾先后多次去济南、北京等医院就诊 ,诊断为良性假肥大型肌营养不良。家系调查 :调查 6代 ,患者 13人 ,均为男性。临床表现与先证者相同 ,但程度不同。已死亡 5人 ,死亡年龄 5 1～ 62岁 ,发病年龄最小 7岁 ,最大 2 0岁 (图 1)。图 1　患者家系…     

假肥大型肌营养不良基因诊断技术研究进展

假肥大型肌营养不良是由于Dystrophin基因突变而导致的X-连锁隐型遗传病,目前对这种疾病还没有有效的治疗方法。通过基因诊断技术对假肥大型肌营养不良患者以及携带者进行准确、全面的突变检测,进而进行产前诊断避免患儿的出生是目前解决这一问题的最有效途径。近几年来,一些常规的Dystrophin基因突变检测技术有了新的进展,同时也出现了一些全新的技术。该文对几种重要检测技术的研究进展进行综述。     

基于孕前优生平台的育龄女性假肥大型肌营养不良症携带者筛查模式

目的:探索在孕前优生健康检查平台中建立育龄期女性假肥大型肌营养不良(Duchenne muscular dystrophy,DMD)致病基因携带者筛查模式,提高携带者的检出率。方法:应用速率法/紫外分光光度法进行血清酶学检测,对2017年10月至2019年10月在杭州市参加国家免费孕前优生健康检查的61 870名育龄女...     

假肥大型肌营养不良症的基因突变和产前诊断研究

目的 了解中国人群DMD基因外显子突变的特点和产前诊断情况.方法 应用多重连接依赖性探针扩增技术(multiplex ligation-dependent probe amplification,MLPA)和变性高效液相色谱(denaturing high performance liquid chromatography,DHPLC)技术对Duchenne型假肥大型肌营养不良症(Duchenne muscular dystrophy,DMD)患者及胎儿进行DMD基因检测并对结果进行统计分析.结果 在388例DMD患者中发现缺失、重复和点突变3种突变类型,其中缺失突变230例,占59.28％,重复突变43例,占11.08％.共发现2个缺失热点区域,分别涉及第45～54外显子和第3～19外显子.重复突变主要位于第2～43外显子之间.发现点突变115例,占29.64％.对其中6例进行检测共发现5例点突变.在53例产前诊断中,共发现33例男胎,其中18例为患病胎儿.患病家庭在已知同意的前提下自主选择了终止妊娠.结论 中国人DMD基因的突变特点与国外报道一致.产前诊断可避免DMD患儿出生.     

一例罕见的47,XXX女性假肥大型肌营养不良症

患者　女 ,10岁。因走路不稳易摔跤、上楼梯困难及小腿肥大就诊。患儿系足月顺产 ,生长发育较同龄儿童落后 ,智力、发育正常。查体 :神志清楚 ,皮肤巩膜无黄染 ,浅表淋巴结不肿大 ,心脏听诊无异常 ,肝、脾未触及。步态呈鸭步 ,躯干、骨盆和四肢的肌肉萎缩 ,翼状肌、小腿腓肠肌肥大 ,未引出病理反射 ,Gower's征阳性。心电图示心肌损害 ,右肱二头肌和右胫前肌肌电图显示肌源性损害。血液生化检显示患者肌酸激酶 10 10 3U / L (正常参考值 15～ 15 0 U/ L ) ,乳酸脱氢酶 6 4 3U/ L (正常参考值 180～ 4 30 U/ L ) ,谷草转氨酶 14 4 U/ L (…     

假肥大型肌营养不良症与HLA-A、B、DR等位基因的相关性研究

目的研究南方汉族人群中假肥大型肌营养不良症(Duchenne muscular dystrophy,DMD)患者的HLA-A、B、DR基因多态性,探讨免疫遗传因素在DMD发病机制及肌纤维坏死中的作用。方法采用PCR反向序列特异性寡核苷酸杂交技术(polymerase chain reaction-reverse sequence specific oligonucleotide,PCR-RSSO)和美国骨髓库编码软件(National Marrow Donor Program,NMDP),对113例DMD患者和406名健康对照的HLA-A、B、DR等位基因进行多态性分析。结果DMD组HLA-A24、A30等位基因的频率分别为11.25%和5.46%,与对照组的22.16%和0.87%相比差异有统计学意义(P=0.001,<0.01);DMD组HLA-B13、B15、B61、B62等位基因频率12.26%、16.92%、0.44%、0.44%,与对照组6.76%、1.49%、4.79%、5.05%相比差异有统计学意义(P=0.016,<0.01,0.001);DMD组HLA-DR04、DR07、DR12等位基因频率17.45%、6.40%、19.62%,与对照组10.67%、2.24%、11.92%相比差异有统计学意义(P=0.018,<0.01,0.012)。结论DMD患者HLA等基因表达与正常对照组有显著差异,HLA基因型可能与DMD的肌纤维坏死和发病机制相关。     

两家同胞肌营养不良与脊肌萎缩症肌电图分析

肌营养不良(muscular dystrophy)为一组遗传性肌肉疾病。临床过程呈进行性．可在出生时即有，也可出生后数年才发病，大多数是由于原发性肌肉损伤所致．表现为肌纤维的变性。目前公认的诊断方法为根据遗传特点、发病年龄、病肌分布、进展速度以及肌肉变性的程度而确定。肌营养不良主要有四种：①Duchenne型；②Becker型；③面肩肱型；     

Duchenne muscular dystrophy and spinal muscular atrophy type I segregating in the same family

We report on a family with two severe neuromuscular diseases: Duchenne muscular dystrophy (DMD) and acute infantile spinal muscular atrophy (SMA I). One boy has DMD, and his brother died of SMA I at 11 months of age. Both boys had received the same DMD allele from their mother. Analysis of dystrophin by immunohistochemistry and Western blot showed complete lack of dystrophin in both brothers. The mother had a partial deficiency of dystrophin. The boy with SMA I had increased levels of creatine kinase in serum, compatible with DMD, but the muscle biopsy and post-mortem examination of the spinal cord showed the typical changes of SMA I. There were no cytogenetic abnormalities explaining the occurrence of both DMD and SMA I in this family. Molecular genetic prenatal diagnosis of DMD and SMA I, using analysis of RFLPs and dinucleotide repeats, has been performed in one foetus in the family. The results showed that the foetus had a high risk of developing SMA I. An abortion was planned but the pregnancy was terminated by miscarriage.     

Duchenne肌营养不良的基因治疗研究进展

Duchenne肌营养不良（DMD）为X连锁常见的神经肌肉遗传病之一，由于骨骼肌肌膜上的抗肌萎缩蛋白完全或部分缺失引起。不幸的是，从发现这种疾病以来已经历经大约150年，但是还是不可治愈。然而，20年前DMD基因的发现却大大地改变了这种疾病的发展状况。最近，基因治疗的研究取得了较大的进展。本文就DMD的基因治疗的进展加以综述。     

Parental stress in mothers of boys with duchenne muscular dystrophy

OBJECTIVE: To examine parental stress in mothers of boys with Duchenne muscular dystrophy (DMD). METHOD: Stress and its predictors were examined in mothers of boys with DMD (n = 112). Comparisons were made with mothers of healthy children (n = 800), children with cerebral palsy (CP; n = 28), siblings of boys with DMD (n = 46), and longitudinally (n = 16). RESULTS: The presence of problem child behaviors consistently predicted maternal stress. Stress related to child behavior was higher in the DMD versus the normative group. No differences in stress were found in the DMD versus CP groups. Stress related to boys with DMD versus siblings was not significantly different. Over time, maternal stress related to child variables diminished. CONCLUSION: Stress in mothers of boys with DMD is elevated, possibly due to increased problem behaviors, particularly in social interactions, rather than due to the physical demands of the disease alone.     

Serum levels of myoglobin and creatine kinase in duchenne muscular dystrophy

Summary Using a sensitive myoglobin-radioimmunoassay (Mb-RIA) serum Mb was measured in 50 patients with Duchenne muscular dystrophy (DMD) and compared with the serum creatine kinase (CK) activities. The Mb concentrations (normal range 4–60 ng/ml) measured ranged between 160–6,000 ng/ml and did not only show a significant correlation to the CK but also an inverse relationship to the age of the patients. It is suggested that Mb is an essential adjunct in the diagnosis of DMD.     

Capping of lymphocytes in patients and carriers of duchenne muscular dystrophy

Summary Recent results showed that Duchenne muscular dystrophy is probably associated with a generalized membrane defect. The capping phenomenon in lymphocytes indicates normal intramembrane protein mobility and disturbances of this phenomenon are is believed to reflect membrane alterations. We have investigated capping in lymphocytes from 19 patients with Duchenne muscular dystrophy, 13 carriers, 8 patients' sisters, 14 patients' aunts and 52 normal controls. All 19 patients showed a reduction in capping both with fluorescein conjugated polyvalent goat antiserum (mean±SD=18.5±5.2%) and with fluorescein labeled Concanavalin A (mean±SD=10.8±3.2%) as compared to controls. Normal persons (n=52) have a mean of 50.2±9.9% (SD) capping with polyvalent anti-immunoglobulin (range: 32–72.5%) and 25.6±3.6% with F-Con A (range: 18.5–31.5%). 12 of the 13 mothers, as well as 5 of the 8 patients' sisters, also exhibited decreased lymphocyte capping to the same extent as the patients. Creatine kinase activity (CK) was elevated only in 4 mothers and 2 of the sisters. Our results indicate that this method might be of value in detecting carriers and can yield less false negative results as the CK-activity test.Supported in part by Karl- und Maria-Biesinger-Stiftung, Hirschhorn, FRG, and Tumorzentrum Heidelberg/Mannheim, FRG     

A case of atypical duchenne type muscular dystrophy with fragile X

Summary The patient was a 9-year-old boy. He began to walk at the age 1 year and 8 months and began to speak at the age of 2 years, suggesting retarded mental and motor development. A diagnosis of DMD was made when he was 7 years old. On admission, the patient exhibited a peculiar thin and long face, large auricles, narrow palate, malalignment of the teeth, epicanthus, saddle nose, and simian lines in addition to symptoms consistent with DMD. Chromosome analysis showed fragile X at Xq27 at a frequency of 20%. His mother also showed fragile X at the same position. Since the atypical features of this DMD patient are all explained as fragile X syndrome, this case was considered to be a very rare instance of DMD whose clinical pictures were modified by fragile X syndrome.     

The effect of parental age on rate of mutation for duchenne muscular dystrophy

The effect of parental age on mutation rates at the Duchenne Muscular Dystrophy (DMD) locus was studied in 514 male probands who constitute two thirds of the known patients in Japan. We were unable to detect an effect of maternal age at birth of proband or maternal grandfather's age at birth of the mother of the proband on the rate of DMD mutations. The result supports an observation on the hemophilia gene.     

90个脊髓性肌萎缩家系的遗传学分析

目的对90个脊髓性肌萎缩(spinal muscular atrophy,SMA)家系进行基因诊断与产前诊断,为SMA的遗传学分析方法提供参考,并初步探讨SMA缺陷基因携带者基因筛査的必要性。方法应用多重连接探针扩增(multiplex ligation dependent probe amplification,MLP A)技术对90个SMA家系进行基因诊断,联合MLPA及等位基因特异性PCR(allele specific PCR,A&PCR)技术对家系进行产前诊断并对产前诊断结果进行分析。结果在90个SMA家系中,84对夫妻无SMA家族史,占比93%;85对夫妻有SMA生育史,占比94%;85个家系夫妻双方及3个家系的孕妇SMN1基因杂合缺失,为SMA缺陷基因携带者;2个家系孕妇SMN1基因纯合缺失,为SMA患者;产前诊断结果显示48名胎儿为SMA缺陷基因携带者,23名胎儿为正常胎儿,19名胎儿为SMA患者,其中无家族史夫妻双方再孕SMA胎儿18例,占总SMA胎儿95%、占总胎儿20%。结论应用MLPA对夫妻双方进行SMA缺陷基因携带者筛查,并联合使用MLPA和AS-PCR对携带者夫妻进行SMA产前诊断十分必要,对预防SMA出生缺陷具有积极意义。     

Genotyping of spinal muscular atrophy families with linked DNA probes

We report on linkage analysis and haplotype characterization in 40 Italian families with spinal muscular atrophy (SMA). The investigated loci included D5S6, D5S112, D5S39, and D5S76. No evidence of unlinked families was found. Thirty-two (80%) of the examined families were fully informative for prenatal diagnosis and carrier detection. The frequencies of individual alleles did not differ between SMA and normal chromosomes.     

脊髓性肌萎缩症基因诊断研究进展

脊髓性肌萎缩症是一组常染色体隐性遗传病,临床表现为进行性肌无力、肌萎缩,是导致婴儿死亡最常见的疾病之一。脊髓性肌萎缩症的致病基因被定位于染色体5q13．2,此外还发现其他多种基因与其临床表型相关。对该病进行基因诊断可以明确病因,预防患儿出生。此文对该病的最新基因学及基因诊断学进展作一综述。