BACKGROUND Spinal muscular atrophy (SMA) is a neuromuscular disease caused by homozygous deletion of SMN1 exons 7 and 8. However, exon 8 is retained in some cases, where SMN2 exon 7 recombines with SMN1 exon 8, forming a hybrid SMN gene. It remains unknown how the hybrid SMN gene contribute to the SMA phenotype. METHOD We analyzed 515 patients with clinical suspicion for SMA. SMN1 exons 7 and 8 deletion was detected by PCR followed by enzyme digestion. Hybrid SMN genes were further analyzed by nucleotide sequencing. SMN2 copy number was determined by real-time PCR. RESULTS SMN1 exon 7 was deleted in 228 out of 515 patients, and SMN1 exon 8 was also deleted in 204 out of the 228 patients. The remaining 24 patients were judged to carry a hybrid SMN gene. In the patients with SMN1 exon 7 deletion, the frequency of the severe phenotype was significantly lower in the patients with hybrid SMN gene than in the patients without hybrid SMN gene. However, as for the distribution of SMN2 exon 7 copy number among the clinical phenotypes, there was no significant difference between both groups of SMA patients with or without hybrid SMN gene. CONCLUSION Hybrid SMN genes are not rare in Japanese SMA patients, and it appears to be associated with a less severe phenotype. The phenotype of patients with hybrid SMN gene was determined by the copy number of SMN2 exon 7, as similarly for the patients without hybrid SMN gene.

中文翻译：

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混合型SMN基因脊髓性肌萎缩症患者的临床表型

背景技术脊髓性肌萎缩症(spinal muscular atrophy，SMA)是一种由SMN1外显子7和8纯合缺失引起的神经肌肉疾病。然而，在某些情况下，外显子8仍保留，其中SMN2外显子7与SMN1外显子8重组，形成杂交SMN基因。杂种 SMN 基因如何促成 SMA 表型仍然未知。方法 我们分析了 515 名临床怀疑患有 SMA 的患者。通过 PCR 和酶切检测 SMN1 外显子 7 和 8 缺失。杂交 SMN 基因通过核苷酸测序进一步分析。SMN2 拷贝数由实时 PCR 确定。结果 515 名患者中有 228 名 SMN1 外显子 7 被删除，228 名患者中有 204 名 SMN1 外显子 8 也被删除。其余 24 名患者被判断为携带杂交 SMN 基因。在 SMN1 外显子 7 缺失的患者中，有杂交SMN基因的患者重度表型的频率明显低于无杂交SMN基因的患者。然而，对于SMN2外显子7拷贝数在临床表型中的分布，有或没有杂交SMN基因的两组SMA患者之间没有显着差异。结论 杂种 SMN 基因在日本 SMA 患者中并不罕见，它似乎与不太严重的表型相关。具有杂交 SMN 基因的患者的表型由 SMN2 外显子 7 的拷贝数决定，与没有杂交 SMN 基因的患者类似。有或没有杂交SMN基因的两组SMA患者之间没有显着差异。结论 杂种 SMN 基因在日本 SMA 患者中并不罕见，它似乎与不太严重的表型相关。具有杂交 SMN 基因的患者的表型由 SMN2 外显子 7 的拷贝数决定，与没有杂交 SMN 基因的患者类似。有或没有杂交SMN基因的两组SMA患者之间没有显着差异。结论 杂种 SMN 基因在日本 SMA 患者中并不罕见，它似乎与不太严重的表型相关。具有杂交 SMN 基因的患者的表型由 SMN2 外显子 7 的拷贝数决定，与没有杂交 SMN 基因的患者类似。