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目的以中国西南地区汉族人群为研究对象,构建脊肌萎缩症(SMA)相关基因拷贝数变化频率,为SMA的临床诊断和分型提供依据。方法收集62例临床诊断为SMA的无亲缘关系患者,以及50例无亲缘关系的正常人作为健康对照组,采用多重连接酶依赖的探针扩增技术(MLPA)分析运动神经元基因(SMN)和神经原凋亡抑制蛋白基因(NAIP)的拷贝数。结果 62例患者中,SMAⅠ~Ⅳ型分别占30.65%(19/62)、41.94%(26/62)、16.13%(10/62)、11.29%(7/62)。SMN1基因外显子7纯合缺失占98.38%(61/62),SMN1基因外显子8纯合缺失占82.26%(51/62)。SMAⅠ型患者中NAIP基因外显子5有68.42%(13/19)纯合缺失,26.32%(5/19)杂合缺失;SMAⅡ~Ⅳ型患者中NAIP基因外显子5有13.95%(6/43)纯合缺失,62.79%(27/43)杂合缺失。SMAⅠ型患者中68.42%(13/19)有1~2拷贝的SMN2基因,SMAⅡ型中84.62%(22/26)有2拷贝以上的SMN2基因,90.00%(9/10)SMAⅢ型和85.71%(6/7)SMAⅣ型患者有2拷贝以上的SMN2基因,且发现有5拷贝和6拷贝SMN2基因。结论 SMN1基因缺失是SMA的主要致病原因,SMN2和NAIP基因拷贝数变化可以影响SMA病情严重程度。
Objective To construct the frequencies of SMA related gene copy number changes in Chinese Han population in Southwest China and provide evidence for the clinical diagnosis and typing of SMA. Methods Totally 62 unrelated patients with clinically diagnosed SMA and 50 unrelated healthy controls were enrolled in this study. Motor neuron gene (SMN) was analyzed by multiplex ligase-dependent probe amplification (MLPA) And the copy number of the neuronal apoptosis-inhibitory protein gene (NAIP). Results Among 62 patients, SMA Ⅰ ~ Ⅳ accounted for 30.65% (19/62), 41.94% (26/62), 16.13% (10/62) and 11.29% (7/62) respectively. The homozygous deletion of exon 7 of SMN1 gene accounted for 98.38% (61/62), while the homozygous deletion of exon 8 of SMN1 gene accounted for 82.26% (51/62). There were 68.42% (13/19) homozygous deletions in NAI gene exon 5 and 26.32% (5/19) heterozygous deletion in SMA type Ⅰ patients; 13.95% (13.95%) of NAIP exon 5 in SMA Ⅱ ~ Ⅳ patients / 43) homozygous deletion, 62.79% (27/43) heterozygous deletion. There were 1 to 2 copies of SMN2 gene in 68.42% (13/19) of patients with SMA type Ⅰ, more than 2 copies of SMN2 gene in 84.62% (22/26), 90.00% (9/10) of SMA Ⅲ type and 85.71% (6/7) There are two copies of the SMN2 gene in SMA type IV patients, and five copies and six copies of the SMN2 gene are found. Conclusion The deletion of SMN1 gene is the main cause of SMA. The changes of SMN2 and NAIP gene copy number may affect the severity of SMA.