Programa de Diagnòstic Molecular de Càncer Hereditari, Laboratori de Recerca Translacional, Institut Català d'Oncologia-Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
Eur J Hum Genet. 2010 May;18(5):614-7. doi: 10.1038/ejhg.2009.212. Epub 2009 Nov 25.
Neurofibromatosis type 1 is one of the most common neurocutaneous autosomal dominant disorders. It is caused by mutations in the neurofibromatosis type 1 (NF1) gene and approximately 30-40% of them affect the correct splicing of NF1 pre-mRNA. In this report, we evaluate the effect of five different drugs, previously found to modify splicing in several genetic disorders, on the splicing of mutated NF1 alleles. For this purpose, cell lines derived from patients bearing 19 different NF1-splicing defects were used. Our results showed that kinetin partially corrects the splicing defect in four of the studied mutations (c.910C>T, c.3113G>A, c.6724C>T and c.6791dupA). Our study is a valuable contribution to the field because it identifies new exon-skipping events that can be reversed by kinetin treatment and provides new information about kinetin splicing modulation. However, owing to the nature of mutations in our patients, kinetin treatment could not be used as a therapeutic agent in these cases.
神经纤维瘤病 1 型是最常见的神经皮肤常染色体显性遗传病之一。它是由神经纤维瘤病 1 型（NF1）基因突变引起的，约 30-40%的突变会影响 NF1 前体 mRNA 的正确剪接。在本报告中，我们评估了之前在几种遗传疾病中发现可改变剪接的五种不同药物对突变 NF1 等位基因剪接的影响。为此，使用了源自携带 19 种不同 NF1 剪接缺陷的患者的细胞系。我们的结果表明，激动素可部分纠正所研究的四种突变（c.910C>T、c.3113G>A、c.6724C>T 和 c.6791dupA）中的剪接缺陷。我们的研究是该领域的一项有价值的贡献，因为它确定了新的外显子跳跃事件，激动素处理可逆转这些事件，并提供了关于激动素剪接调节的新信息。然而，由于我们患者的突变性质，激动素治疗不能在这些情况下用作治疗剂。
