Department of Community Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine, Kobe, Japan.
Department of Community Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine, Kobe, Japan; Faculty of Medical Rehabilitation, Kobe Gakuin University, Kobe, Japan.
Brain Dev. 2021 Feb;43(2):294-302. doi: 10.1016/j.braindev.2020.09.005. Epub 2020 Oct 6.
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.
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.
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.
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.
脊髓性肌萎缩症（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 被保留，其中 SMN2 外显子 7 与 SMN1 外显子 8 重组，形成杂交 SMN 基因。目前尚不清楚杂交 SMN 基因如何导致 SMA 表型。
我们分析了 515 例具有 SMA 临床可疑症状的患者。通过 PCR 后酶消化检测 SMN1 外显子 7 和 8 的缺失。进一步通过核苷酸测序分析杂交 SMN 基因。通过实时 PCR 确定 SMN2 拷贝数。
515 例患者中，228 例患者 SMN1 外显子 7 缺失，204 例患者 SMN1 外显子 8 也缺失。其余 24 例患者被判断携带杂交 SMN 基因。在 SMN1 外显子 7 缺失的患者中，携带杂交 SMN 基因的患者严重表型的频率明显低于不携带杂交 SMN 基因的患者。然而，对于具有 SMN1 外显子 7 缺失的患者，临床表型之间 SMN2 外显子 7 拷贝数的分布没有显著差异。
在日本 SMA 患者中，杂交 SMN 基因并不罕见，并且似乎与较轻的表型相关。与不携带杂交 SMN 基因的患者一样，携带杂交 SMN 基因的患者的表型由 SMN2 外显子 7 的拷贝数决定。
