摘要目的 确定运动神经元存活基因1(survival motor neuron gene 1,SMN1)纯合缺失在中国脊肌萎缩症(spinal muscular atrophy,SMA)患儿中的发生频率,判断SMN1基因纯合缺失检测在中国SMA患儿诊断中的临床价值,探讨基因检测后的临床回访在SMA疑诊患儿临床诊疗中的作用.方法 使用多聚酶链反应和限制性片段长度多态性的方法 (polymerase chain reaction and restriction fragment length polymorphism,PCR-RFLP)对85例临床疑诊SMA的患儿样本进行SMN1基因7号外显子纯合缺失检测.由小儿神经专科医师对SMA患儿进行分型,并对基因检测阴性的患儿依照SMA的诊断标准,必要时结合组织学病理检查进行临床再评估.结果 在85例中,57例(67%)检出SMN1纯合缺失.在19例随访的基因检测阴性患儿中,15例不符合SMA的诊断,4例可维持SMA的诊断.在确诊的SMA患儿中,SMN1纯合缺失率为95%.Ⅰ、Ⅱ、Ⅲ型SMA患儿的SMN1纯合缺失检出率分别为96%、93%和100%,SMA临床分型与SMN1纯合缺失率无显著相关性.结论 中国SMA患儿中SMN1基因纯合缺失约为95%,与高加索人群数据相似.SMN1纯合缺失检测应成为中国SMA疑诊患儿的首选诊断和排除诊断方法 .SMN1纯合缺失检测后患儿的临床回访对SMA疑诊患儿的临床诊疗具有重要意义.

abstractsObjective Spinal muscular atrophy(SMA),characterized by degeneration of the anterior horn cells in the spinal cord and symmetric proximal muscle weakness,is the most common autosomal recessive neuromuscular disease in infants and children.In Caucasian population,about 95%of clinically typical patients lack both copies of the telomeric survival motor neuron gene(SMN1).However,the detection rate of the homozygous absence in Chinese patients is still controversial,which may lead to reduced confidence in the SMA genetic testing in clinical practice.The purpose of the current study was to determine the frequency of homozygous deletions of SMN1 in Chinese patients,to evaluate the significance of the SMN1 homozygous deletion assay in clinical applications.and the impact of the chinical re-visit followed by the genetic testing.Methods Totally 85 patients initially suspected of SMA were referred for SMA genetic testing.A polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP)assay was used to detect the homozygous absence of SMN1.Clinical re-visit was performed by the pediatric neurology specialists according to the international SMA diagnostic criteria,and histological examinations were carried out when they were necessary.Results Absence of both copies of SMN1 exon 7 were found in 57(67%)of the 85 patients,and 28 patients(33%)had at least one copy.For the 28 patients with negative results,19 were followed up by the pediatric neurologists.The clinical diagnosis of SMA could be excluded in 15 patients.but retained in the other 4 patients after the clinical re-evaluation and histological examinations.Thus,approximately 95% of the patients with clinically typical SMA in our cohort lacked both copies of SMN1.Homozygous deletions of SMN1 were detected in 96%(22/23),93%(28/30) and 100% (7/7)of the patients with SMA type Ⅰ,type Ⅱ and type Ⅲ,respectively.There was no significant difference in the deletion frequency among the subtypes.Conclusions The frequency of homozygous deletions of SMN1 in the series of Chinese SMA patients was about 95%,which is similar to that reported in Caucasian population. The genetic test of homozygous deletions of SMN1 should be considered as the first line test for the Chinese patients suspected of SMA. The clinical re-visit and re-evaluation which is essential in clinical diagnosis, genetic counseling and medical management, should be routinely performed after the genetic testing.