{"doi":"10.1186/1471-2350-8-4","title":"Functional analysis of splicing mutations in exon 7 of NF1gene","abstract":"<jats:title>Abstract</jats:title>\n          <jats:sec>\n            <jats:title>Background</jats:title>\n            <jats:p>Neurofibromatosis type 1 is one of the most common autosomal dominant disorders, affecting about 1:3,500 individuals. <jats:italic>NF1</jats:italic> exon 7 displays weakly defined exon-intron boundaries, and is particularly prone to missplicing.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Methods</jats:title>\n            <jats:p>In this study we investigated the expression of exon 7 transcripts using bioinformatic identification of splicing regulatory sequences, and functional minigene analysis of four sequence changes [c.910C&gt;T (R304X), c.945G&gt;A/c.946C&gt;A (Q315Q/L316M), c.1005T&gt;C (N335N)] identified in exon 7 of three different <jats:italic>NF1</jats:italic> patients.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Results</jats:title>\n            <jats:p>Our results detected the presence of three exonic splicing enhancers (ESEs) and one putative exonic splicing silencer (ESS) element. The wild type minigene assay resulted in three alternative isoforms, including a transcript lacking <jats:italic>NF1</jats:italic> exon 7 (NF1ΔE7). Both the wild type and the mutated constructs shared NF1ΔE7 in addition to the complete messenger, but displayed a different ratio between the two transcripts. In the presence of R304X and Q315Q/L316M mutations, the relative proportion between the different isoforms is shifted toward the expression of NF1ΔE7, while in the presence of N335N variant, the NF1ΔE7 expression is abolished.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion</jats:title>\n            <jats:p>In conclusion, it appears mandatory to investigate the role of each nucleotide change within the <jats:italic>NF1</jats:italic> coding sequence, since a significant proportion of <jats:italic>NF1</jats:italic> exon 7 mutations affects pre-mRNA splicing, by disrupting exonic splicing motifs and modifying the delicate balance between aberrantly and correctly spliced transcripts.</jats:p>\n          </jats:sec>","journal":"BMC Medical Genetics","year":2007,"id":32579,"datarank":2.0182305175337634,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"self_citation_contribution":0.5456379239589579,"citation_network_contribution":1.4725925935748052,"self_endowment_contribution":0.5456379239589579,"citer_contribution":1.4725925935748052,"corpus_percentile":null,"corpus_rank":null,"citation_count":37,"citer_count":33,"citers_with_citation_signal":27,"citers_with_endowment":27,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":172148,"name":"Alessandro De Luca","orcid":null,"position":1,"is_corresponding":false},{"id":172149,"name":"Annalisa Schirinzi","orcid":null,"position":2,"is_corresponding":false},{"id":172150,"name":"Valentina Guida","orcid":null,"position":3,"is_corresponding":false},{"id":172151,"name":"Isabella Torrente","orcid":null,"position":4,"is_corresponding":false},{"id":172153,"name":"Stefano Calvieri","orcid":null,"position":5,"is_corresponding":false},{"id":172155,"name":"Cristina Gervasini","orcid":null,"position":6,"is_corresponding":false},{"id":172157,"name":"Lidia Larizza","orcid":null,"position":7,"is_corresponding":false},{"id":172158,"name":"Antonio Pizzuti","orcid":null,"position":8,"is_corresponding":false},{"id":17512,"name":"Bruno Dallapiccola","orcid":"0000-0002-5031-1013","position":9,"is_corresponding":false},{"id":172147,"name":"Irene Bottillo","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17295913","pmcid":"PMC1802069","openalex_id":"https://openalex.org/W1579564476","authors":[],"funders":[],"total_grants":0,"fwci":1.9124,"citation_percentile":0.84754687,"influential_citations":1,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":4},{"year":2015,"count":3},{"year":2016,"count":1},{"year":2017,"count":2},{"year":2018,"count":5},{"year":2020,"count":2},{"year":2021,"count":5},{"year":2024,"count":1},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://bmcmedgenet.biomedcentral.com/counter/pdf/10.1186/1471-2350-8-4","host_type":"journal"},{"url":"https://bmcmedgenet.biomedcentral.com/counter/pdf/10.1186/1471-2350-8-4","host_type":"GOLD"},{"url":"https://bmcmedgenet.biomedcentral.com/counter/pdf/10.1186/1471-2350-8-4","host_type":"publisher"},{"url":"http://link.springer.com/content/pdf/10.1186/1471-2350-8-4.pdf","host_type":"publisher"},{"url":"http://link.springer.com/article/10.1186/1471-2350-8-4/fulltext.html","host_type":"publisher"},{"url":"http://link.springer.com/content/pdf/10.1186/1471-2350-8-4","host_type":"publisher"},{"url":"https://link.springer.com/content/pdf/10.1186/1471-2350-8-4.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1186/1471-2350-8-4","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17295913","host_type":"repository"},{"url":"http://hdl.handle.net/2434/28690","host_type":"repository"},{"url":"https://doaj.org/article/dad1405eab304167adbde88bf7fe8172","host_type":"repository"},{"url":"https://hdl.handle.net/11573/362642","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1802069","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC1802069","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC1802069?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Neurofibromatosis and Schwannoma Cases","Hereditary Neurological Disorders","Dupuytren's Contracture and Treatments","Biology","Medicine","Alternative Splicing","DNA Mutational Analysis","Exons","Genes, Neurofibromatosis 1","Humans","Neurofibromatosis 1","Polymerase Chain Reaction","RNA Precursors"],"mesh_terms":["DNA Mutational Analysis","Exons","Humans","Neurofibromatosis 1","RNA Precursors","Polymerase Chain Reaction","Genes, Neurofibromatosis 1","Alternative Splicing"],"keywords":["Minigene","Exon","RNA splicing","Exonic splicing enhancer","Biology","Genetics","Intron","Alternative splicing","Exon trapping","Polypyrimidine tract","Enhancer","Exon skipping","Molecular biology","Gene","Gene 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