疑似脊髓性肌萎缩症患儿338例的运动神经元存活基因分析

目的 研究儿童脊髓性肌萎缩症(SMA)运动神经元存活基因SMN1缺失和诊断的意义.方法 根据国际诊断标准、病例随访和基因分析结果对338例疑似SMA的患儿进行诊断和分型.应用PCR-酶切方法分析患儿SMN1基因外显子7和外显子8的纯合缺失.应用等位基因特异PCR结合变性高效液相色谱分析(DHPLC)方法分析患儿的SMN1基因拷贝数,确定杂合缺失.结果 (1)确诊SMA 267例,其中Ⅰ型143例,Ⅱ型82例,Ⅲ型42例,分别占53.6%、30.7%和15.7%.(2)267例SMA患儿的SMN1基因缺失分析显示:SMN1基因外显子7和8均纯合缺失为183例,占68.5%(183/267),仅外显子7纯合缺失,外显子8不缺失为34例,占12.7%(34/267),外显子7杂合缺失为33例,占12.4%(33/267),非缺失为17例,占6.4%(17/267),未见SMN1基因外显子8的单独缺失.(3)Ⅰ型和Ⅱ型SMN1基因缺失率相近.Ⅲ型SMN1基因纯合缺失率较低于Ⅰ型和Ⅱ型,杂合缺失率较高于Ⅰ型和Ⅱ型.结论 (1)我国儿童SMA的SMN1基因纯合缺失和杂合缺失频率提示,SMN1基因突变存在种族异质性,SMN1基因内微小突变需要研究.(2)SMN1基因诊断具有特异性和无创性,80%SMA患儿通过SMN1基因纯合缺失分析得到诊断.(3)Ⅲ型SMA的临床诊断和基因分析需要进一步研究.     

儿童脊髓性肌萎缩症的基因诊断

目的探讨儿童脊髓性肌萎缩症(SMA)的特异性基因诊断方法。方法应用聚合酶链反应-限制性片段长度多态性(PCR—RFLP)技术.对19例临床诊断为SMA患儿及21名健康儿童的运动神经元存活(SMN)基因进行检测。结果SMA患儿SMN基因的第7和第8号外显子均缺失,健康儿童SMN基因的第7和第8号外显子均未缺失。结论检测SMN基因第7和第8号外显子缺失的方法可用于SMA的基因诊断,且PCR—RFLP技术对SMA的诊断具有较高的特异性和敏感性。     

脊髓性肌萎缩症及临床相关SMN基因的研究进展

该文主要阐述了脊髓性肌萎缩症的主要临床特点和疾病相关SMN基因的研究进展。脊髓性肌萎缩症是一种遗传性主要累及肢体近端的肌麻痹、肌萎缩;部分患者可伴有少数非特异症状和体征。肌电图、神经电图、肌活检等辅助检查对该病的诊断和鉴别诊断有重要作用;基因检测是目前认为有效的确诊该病的辅助手段;诱发电位检查在该病的I型患儿中亦有改变。目前,临床对该病主要是对症治疗和预防并发症的发生。产前诊断是预防该病患儿出生的主要手段。该文同时对疾病相关SMN基因的结构与表型相关性,SMN蛋白的功能和基因治疗研究进展进行阐述。     

脊髓性肌萎缩症患儿营养管理研究进展

脊髓性肌萎缩症(SMA)是一种严重的神经肌肉疾病,因运动神经元存活基因1(SMN 1)缺陷引起.由于肌肉无力、活动量少、消化道症状以及吞咽困难等原因,患儿发生营养不足和营养过剩的概率常明显高于正常儿童,因此SMA的营养管理至关重要.文章就SMA患儿的营养评估、可能出现的营养问题以及相关营养干预策略进行阐述.     

小儿脊髓性肌萎缩的分子遗传学研究进展

小儿脊髓性肌萎缩是第二位常见的致死性常染色体隐性遗传病,具有三种临床类型,近年来该的致病基因被定位于５ｑ１１－５ｑ１３区域,目前发现与该病有关的基因有运动神经元存活基因,神经元调亡抑制蛋白基因和编码Ｐ４４蛋白基因,本文对该病的最新分子遗传学进展作一综述。     

小儿脊髓性肌萎缩

脊髓性肌萎缩是一组常染色体隐性(AR)遗传的进行性并通常为对称性肌无力与萎缩的疾病.5q型常见,由5q13 上SMNI基因缺失(95%的病例)或突变(约5%的病例)引起.分为4型.18个月内起病的Ⅰ型与Ⅱ型往往因呼吸吞咽不良、不能站坐走与继发骨折等而坝后严重.非-5q型为一组异源性运动神经元病,临床表现与前者有所不同.5q型的诊断根据病史、血清肌酶、肌电图、肌活检而确诊靠基因检查,如纯合子缺失用PCR-SSCP等检测、点突变用点突变序列检测.胎儿细胞基因检测可提供产前诊断.治疗是多方面的.对症治疗与支持治疗要求有关各科专家积极合作.随着医疗技术的进步.患者的寿命与活动状况均有改进.分子治疗已初露曙光.     

脊髓性肌萎缩症的基因诊断和SMN基因定量分析研究进展

脊髓性肌萎缩症是一种常染色体隐性遗传病,主要表现为进行性、对称性肢体近端和躯干肌肉无力、萎缩.其致病基因定位于5q13,共有四个候选基因,其中SMN基因为致病基因,其他三个基因是修饰基因.基因诊断是目前比较可靠且运用较多的辅助检查方法.SMN基因定量分析可以作为预测疾病严重程度的指标以及基因诊断和检测携带者的补充.该文对四个候选基因的结构和功能、基因诊断及SMN基因定量分析方面的研究进展作一综合性描述.     

脊髓性肌萎缩症患儿SMN1和SMN2基因拷贝数与临床表型的相关性分析

目的 对脊髓性肌萎缩症（SMA）患儿的运动神经元存活基因1（SMN1）和SMN2拷贝数与临床表型之间的关系进行分析,提高对SMA患儿的早期诊断和临床干预水平。方法 选取45例SMA患儿,应用多重连接依赖性探针扩增技术对SMN1和SMN2基因拷贝数进行检测,分析SMN基因拷贝数同临床表型之间的关系。结果 45例SMA患儿中,SMN1第7和8外显子纯合缺失者为42例,占93%（42/45）;仅有第7外显子缺失者为3例,占7%（3/45）。SMA不同临床分型和SMN1基因第7、8外显子缺失类型间无相关性（P > 0.05）;SMA患儿和健康儿童的SMN2基因拷贝数分布差异有统计学意义（P < 0.05）,前者以2和3拷贝者居多,后者以1和2拷贝者居多;不同SMA临床分型间SMN2拷贝数分布差异有统计学意义（P < 0.05）,SMN2基因为2拷贝者发病年龄明显小于3和4拷贝者。Ⅰ型SMA患儿中SMN2拷贝数以2或3拷贝者居多,Ⅱ型以3拷贝者居多,Ⅲ型以3或4拷贝者居多。随着SMN2拷贝数增加,患儿发病年龄越大,保有的运动功能和临床结局越好,SMN2基因拷贝数同临床结局间的关系存在显著性差异（P < 0.05）。结论 SMN2基因通过剂量补偿效应减轻SMA疾病严重程度,SMN2拷贝数同SMA临床表型具有相关性,可将其作为预测疾病严重程度的依据之一。     

117例儿童脊髓性肌萎缩症自然病史分析

目的 对重庆及周边地区脊髓性肌萎缩症（spinal muscular atrophy,SMA）的自然病史进行分析,为开展SMA的综合管理、基因修饰治疗提供临床依据。 方法 回顾性分析117例SMA患儿的临床资料及生存现状。 结果 117例患儿中,1型SMA 62例（53.0%）、2型45例（38.5%）、3型10例（8.5%）,中位起病年龄分别为2、10、15月龄。1型SMA起病、就诊、确诊时间均早于2、3型SMA（P<0.05）,1型SMA就诊时间窗（起病年龄至就诊年龄）短于2、3型SMA（P<0.05）。肺炎为首发症状、抬头无力、哭声无力、进食费力多见于1型SMA（P<0.05）,2型SMA脊柱侧弯和下肢关节挛缩发生率高于1型（P<0.05）。117例（100%）SMA患儿均为SMN1基因纯合缺失,其中以7号外显子纯合缺失最常见（68.4%,80/117）。1型SMA的6年生存率仅为10%±5%,低于2、3型SMA（P<0.05）。起病年龄≤3月龄、肺炎为首发症状、抬头无力为1型SMA死亡的危险因素（P<0.05）。2型SMA运动能力可呈非线性倒退。 结论 各型SMA患儿临床表现、生存率均存在异质性,1型SMA生存率低,2型SMA运动能力可呈非线性倒退,临床上应早期识别及管理SMA。     

复合杂合变异脊髓性肌萎缩症1例报告

脊髓性肌萎缩症是一种常染色体隐性遗传病,常规基因诊断方法无法检出隐性遗传病携带者,易造成诊断延误,加重家庭及社会负担.先证者,男性,2月龄,生后哭声低弱、四肢无力,肌电图示脊髓前角细胞病变.采取多重连接探针扩增技术、长片段PCR扩增、连锁分析诊断患儿SMN 1基因为1 d+0型复合杂合变异(1 d:c.22_23 ...     

儿童脊肌萎缩症23例临床特点及遗传学分析

目的 探讨脊肌萎缩症的临床特点和遗传方式。方法 对23例脊肌萎缩症患儿的临床资料进行总结,并用Weiber先证法分析其发病的遗传规律。结果 临床特点为出生后双下肢呈对称性弛缓性瘫痪且进行性加重,四肢近端无力,肌张力、肌力低下;肌电图主要表现为神经原性损害。隐性遗传分离分析表明,12个家系23例患儿发病方式符合常染色体隐性遗传。结论 脊肌萎缩症的临床发病早且病死率高,在遗传咨询中注意作相关产前基因检查,可避免该类患儿的出生。     

脊髓性肌萎缩症合并脊柱侧凸的临床诊治

脊髓性肌萎缩症(SMA)是一种以脊髓前角α运动神经元退行性病变、进行性近端肌无力为特征的严重神经肌肉疾病,随着疾病的进展,还会引发包括骨骼系统、呼吸系统、消化系统等其他多系统疾病,其中脊柱侧凸是最常见的骨骼系统并发症.文章介绍SMA合并脊柱侧凸的自然史,以及不同程度脊柱侧凸的临床保守治疗和手术治疗方法,重点阐述了多学科...     

Pulmonary function and scoliosis in children with spinal muscular atrophy types II and III

Aims:    The objectives were to evaluate the clinical course of spinal muscular atrophy (SMA) types II and III patients necessitating scoliosis surgery at the National University Hospital, Singapore.
Methods:    A retrospective review of SMA types II and III patients, born over a 10-year period between 1983 and 1992, was conducted.
Results:    There were eight patients: four with SMA type II and four with SMA type III. The mean age at scoliosis surgery was 9 years 7 months (range 7 years 6 months−12 years 4 months). The mean preoperative Cobb angle was 65.4° (range 43−90°) and the mean postoperative Cobb angle was 22.6° (range 12−45°), with a mean correction of 64.8% (range 47.7−77.8%). The decline in percentage predicted forced vital capacity (FVC) was 7.7% (95% CI: 12.4% to 3.0%) per year preoperatively and this was reduced to 3.8% (95% CI: 5.8% to 1.9%) per year postoperatively. The mean length of preoperative and postoperative lung function follow-up was 6.3 months (range 0.03−31 months) and 44 months (range 0−110 months), respectively.
Conclusions:    This study suggests that pulmonary function in SMA types II and III continues to decline after scoliosis surgery, though the rate of decline is less marked. Overall, the combined results from this study and all other previously published studies are conflicting in regard to the effect of scoliosis surgery on pulmonary function in SMA types II and IIII, though half of the studies (3 of 6) did demonstrate a continued decline in lung function postoperatively. This decline in pulmonary function despite spinal stabilization is likely secondary to the progressive neuromuscular weakness of the disease.     

Motor nerve conduction studies on children with spinal muscular atrophy

Median and posterior tibial motor nerve conduction studies were performed on 10 children with spinal muscular atrophy (SMA). Three patients with SMA type I, in whom rapid deterioration occurred, showed reduced motor nerve conduction velocity and a remarkably low M-wave amplitude in both nerves. In type II and III patients, the motor nerve conduction velocity was normal in the median nerve, although the M-wave amplitude was small in the tibial nerve. In four patients, a reduction of the M-wave amplitude was observed as clinical symptoms advanced. These findings may suggest that motor conduction studies in spinal muscular atrophy provide complementary information for understanding the pathogenesis and are also useful to clarify the heterogeneity of this disease.     

Molecular analysis of the SMN and NAIP genes in Iranian spinal muscular atrophy patients

Background:  Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of spinal cord anterior horn cells, leading to muscular atrophy. SMA is clinically classified into three subgroups based on the age of onset and severity. The majority of patients with SMA have homozygous deletions of exons 7 and 8 of the survival motor neuron ( SMN ) gene. The purpose of the present study was to determine the frequency of SMN and neuronal apoptosis inhibitory protein ( NAIP ) gene deletions in Iranian SMA patients. Experience in prenatal diagnosis of SMA in this population is also reported.
Methods:  To study the frequency of deletions of SMN and NAIP genes in an Iranian sample group, 75 unrelated SMA patients (54 type I, eight type II and 13 type III) were analyzed according to the methods described by van der Steege et al and Roy et al .
Results:  Homozygous deletion of SMN1 exons 7 and/or 8 were identified in 68 out of 75 patients (90%). Deletion of exon 5 of the NAIP gene was found in 40/54 of type I, 2/8 of type II and 1/13 of type III patients.
Conclusions:  Deletion of the SMN1 gene is a major cause of SMA in Iran, and NAIP gene deletions were common in the present patients with type I SMA. Also, the incidence of NAIP deletion is higher in more severe SMA.     

The role of palliative care in advanced muscular dystrophy and spinal muscular atrophy

OBJECTIVE: This study examines the potential role for palliative care services in the care of individuals with muscular dystrophy and spinal muscular atrophy, and the support of their families. METHODOLOGY: Semistructured interviews were conducted in South Australia with nine bereaved and four current family members of individuals with muscular dystrophy or spinal muscular atrophy. Issues explored during interview included: (i) the family perceptions of the difficulties in caring; (ii) the psychological and physical resources which were available to assist them; and (iii) family recall of the management of the terminal phase of the illness. RESULTS: Significant issues identified included: (i) a lack of coordination of care and access to skilled, competent carers; (ii) a lack of support for siblings; (iii) inadequate bereavement care; and (iv) limited discussion of options of ventilatory support and advance directives. CONCLUSIONS: The terminal care for individuals with muscular dystrophy and spinal muscular atrophy and their families requires improvement. Although many individuals with these conditions will die following an acute event, palliative care services may be appropriate for those who require a period of terminal care at home.