title: Modulation of aberrant NF1 pre-mRNA splicing by kinetin treatment.
abstract: 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.
authors: 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.
authors: Eva
authors: E
authors: Pros
authors: Juana
authors: J
authors: Fernández-Rodríguez
authors: Llúcia
authors: L
authors: Benito
authors: Anna
authors: A
authors: Ravella
authors: Gabriel
authors: G
authors: Capellá
authors: Ignacio
authors: I
authors: Blanco
authors: Eduard
authors: E
authors: Serra
authors: Conxi
authors: C
authors: Lázaro
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects* / Q000235:genetics*; D002460:Cell Line; D006801:Humans; D007701:Kinetin / Q000494:pharmacology*; D025542:Neurofibromin 1 / Q000235:genetics* / Q000378:metabolism; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D025542:Neurofibromin 1; D012322:RNA Precursors; D012333:RNA, Messenger; D007701:Kinetin