van der Steege G, Grootscholten P M, Cobben J M, Zappata S, Scheffer H, den Dunnen J T, van Ommen G J, Brahe C, Buys C H
Department of Medical Genetics, University of Groningen, The Netherlands.
Am J Hum Genet. 1996 Oct;59(4):834-8.
The survival motor neuron (SMN) gene has been described as a determining gene for spinal muscular atrophy (SMA). SMN has a closely flanking, nearly identical copy (cBCD541). Gene and copy gene can be discriminated by sequence differences in exons 7 and 8. The large majority of SMA patients show homozygous deletions of at least exons 7 and 8 of the SMN gene. A minority of patients show absence of SMN exon 7 but retention of exon 8. This is explained by results of our present analysis of 13 such patients providing evidence for apparent gene-conversion events between SMN and the centromeric copy gene. Instead of applying a separate analysis for absence or presence of SMN exons 7 and 8, we used a contiguous PCR from intron 6 to exon 8. In every case we found a chimeric gene with a fusion of exon 7 of the copy gene and exon 8 of SMN and absence of a normal SMN gene. Similar events, including the fusion counterpart, were observed in a group of controls, although in the presence of a normal SMN gene. Chimeric genes as the result of fusions of parts of SMN and cBCD541 apparently are far from rare and may partly explain the frequently observed SMN deletions in SMA patients.
存活运动神经元（SMN）基因已被描述为脊髓性肌萎缩症（SMA）的决定基因。SMN有一个紧密侧翼的、几乎相同的拷贝（cBCD541）。基因和拷贝基因可通过外显子7和8的序列差异来区分。绝大多数SMA患者显示出SMN基因至少外显子7和8的纯合缺失。少数患者显示SMN外显子7缺失但外显子8保留。这可由我们目前对13例此类患者的分析结果来解释，该结果为SMN与着丝粒拷贝基因之间明显的基因转换事件提供了证据。我们不是对外显子7和8的缺失或存在进行单独分析，而是使用了从内含子6到外显子8的连续PCR。在每种情况下，我们都发现了一个嵌合基因，其为拷贝基因的外显子7与SMN的外显子8融合，且正常SMN基因缺失。在一组对照中也观察到了类似事件，包括融合对应物，尽管存在正常的SMN基因。由SMN和cBCD541部分融合产生的嵌合基因显然并不罕见，可能部分解释了在SMA患者中经常观察到的SMN缺失。
