儿童脊髓性肌萎缩症的基因学研究

Study of Genes of Spinal Muscular Atrophy in Children

目的 研究我国儿童型脊髓性肌萎缩症 (SMA)患者的运动神经元生存 (SMN)基因及神经细胞凋亡抑制蛋白 (NAIP)基因外显子的缺失情况 ,以探讨此二种基因与SMA表型之间的关系。方法 应用PCR和PCR -酶切法检测 15例Ⅰ～Ⅲ型SMA患者 (Ⅰ型 4例 ,Ⅱ型 3例 ,Ⅲ型 8例 )、2 0例表型正常的SMA直系亲属及30例正常对照的SMN基因的第 7,8号外显子和NAIP基因的第 5 ,6号外显子缺失情况。结果 7例Ⅰ型和Ⅱ型SMA患者中 6例纯合缺失SMN基因外显子 7和 8,1例纯合缺失外显子 7而保留外显子 8;8例Ⅲ型SMA患者仅1例有外显子 7和 8的缺失 ,余 7例均无SMN基因的缺失 ;15例Ⅰ～Ⅲ型SMA患者均未检测到NAIP基因外显子5和 /或 6的缺失。结论 Ⅰ型、Ⅱ型SMA可通过SMN基因第 7,8号外显子的检测进行确诊 ,方法简便可靠 ,Ⅲ型SMA患者SMN基因缺失率低 ,故通过检测SMN基因 7,8外显子进行基因诊断尚需谨慎 ,NAIP基因在SMA发病中的作用尚不清楚 ,有待进一步研究。

Objective To study the survival motor neuron (SMN) gene exon 7 and 8 and neuronal apoptosis inhibitory protein (NAIP) gene exon 5 and 6 in Chinese patients with Type Ⅰ～Ⅲ SMA, and to confirm the relationship between the deletions of SMN and NAIP genes with SMA phenotype. Methods PCR and PCR-enzyme methods were used to detect the deletions of NAIP gene exon 5 and 6 and SMN gene exon 7 and 8 in 15 SMA (Ⅰ～Ⅲ) patients, 20 healthy relatives and 30 normal controls. Results Deletions of exon 7 and 8 of the telomeric SMN gene were 4/4, 2/3, 1/8 in Type Ⅰ, Ⅱ, Ⅲ SMA patients, respectively. One patient with Type Ⅱ lacked exon 7 but retained exon 8. No deletion was found in the controls (0/50). No deletion of exon 5 and 6 of the NAIP gene was detected in the patients, healthy relatives and controls. Conclusions Deletions of SMN gene exon 7 and 8 examined by PCR-enzyme digestion could be recommended as an accurate gene diagnostic method for SMA with Type Ⅰ and Ⅱ. However, the method was not as useful in Type Ⅲ as in Ⅰ and Ⅱ for the diagnosis of SMA. The frequency of NAIP deletion was lower in Chinese SMA patients.