【摘要】 目的探讨脊髓性肌萎缩症(SMA)的临床表型及基因型特点。方法回顾分析2014年2月至2019年5月确诊的31例脊髓性肌萎缩症患儿的临床资料。结果 31例SMA患儿中,男女比例1.8:1;6月龄内起病12例(38.7%),～18月龄起病17例(54.8%),18月龄后起病2例(6.5%)。首发症状为肌张力低下13例(41.9%),肌力下降9例(29.0%),步态异常5例(16.1%),生长迟缓4例(12.9%)。肌无力主要以近端受累为主,下肢重于上肢,腱反射减弱或消失。在感觉或认知方面均无变化。采用MLPA行基因检测,31例患儿中,SMN1基因外显子7和外显子8纯合缺失29例(93.5%),仅外显子7缺失2例(6.5%),均为2型患儿。不同类型SMA的临床表型与SMN1基因缺失类型之间差异无统计学意义(P>0.05)。2型和3型SMA患儿的SMN2基因拷贝数高于1型,3型SMA患儿的SMN2基因拷贝数明显高于2型,不同SMA临床表型与SMN2拷贝数分布差异有统计学意义(P<0.05)。30例(96.8%)患儿的父母亲明确诊断为SMN1基因杂合缺失;1例患儿父亲明确诊断为SMN1杂合缺失,母亲未检测到。结论 SMN1基因的检测和分析对SMA患儿具有诊断意义。SMA临床表型的严重程度与SMN2基因拷贝数增加呈反比。更多还原

【Abstract】 Objective To investigate the clinical phenotype and genotype characteristics of spinal muscular atrophy (SMA).Methods The clinical data of 31 children with SMA diagnosed from February 2014 to May 2019 were retrospectively analyzed.Results Among the 31 SMA children,the male to female ratio was 1.8:1.The age of onset was as followed:<6 months in 12 cases (38.7%),<18 months in 17 cases (54.8%),and >18 months in 2 cases (6.5%).The initial symptoms were as followed:muscle hypotonia in 13 cases (41.9%),muscle strength decline in 9 cases (29.0%),abnormal gait in 5 cases (16.1%),and growth retardation in 4 cases (12.9%).Myasthenia was mainly found in the proximal body,the lower limb was more serious than the upper limb,and the tendon reflex weakened or disappeared.There was no change in sensation or cognition.The multiplex ligation-dependent probe amplification (MLPA) was used for gene testing.Among the 31 children,29 (93.5%) had homozygous deletion of exon 7 and exon 8 in SMN1 gene,and only deletion of exon 7 was found in 2 children (6.5%),all of whom were type 2.The results showed that there was no significant difference between different phenotypes of SMA and SMN1 gene deletion types (P>0.05).The SMN2 gene copy number of SMA type 2 and 3 was higher than that of SMA type 1,and SMN2 gene copy number of SMA type 3 was significantly higher than that of SMA type 2.The distribution of SMN2 copy number among different SMA phenotypes was statistically significant (P<0.05).The parents of 30 children (96.8%) were found to have loss of heterozygosity of SMN1 gene.In the remaining cases,the father has SMN1 heterozygous deletion,which was not detected by the mother.Conclusions The detection and analysis of SMN1 gene is of diagnostic significance in children with SMA.The clinical phenotypic severity of SMA is inversely proportional to the increase of copy numberof SMN2 gene.更多还原