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In this study, a Chinese <jats:italic>NF1<\/jats:italic> family with an autosomal dominant inheritance pattern was recruited. Exome sequencing and Sanger sequencing were performed to discover the causative variant responsible for the family, followed by molecular analysis of effect of the mutated <jats:italic>NF1<\/jats:italic> protein on Ras activity. A novel frameshift variant c.541dupC (p.(Gln181Profs<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mi>\u2217<\/mml:mi><\/mml:math>20)) in the <jats:italic>NF1<\/jats:italic> gene was identified in all three affected family members. The variant cosegregated with the disease phenotypes in the pedigree and was absent in 100 healthy controls. Bioinformatic analysis showed that the variant c.541dupC (p.(Gln181Profs<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mi>\u2217<\/mml:mi><\/mml:math>20)) was pathogenic. The further molecular analysis verified the cells expressing <jats:italic>NF1<\/jats:italic> variant p.(Gln181Profs<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mi>\u2217<\/mml:mi><\/mml:math>20) partially enhanced Ras activity and elevated cell proliferation and tumor formation due to loss of neurofibromin function caused by the variant. Taken together, the data strongly advocate the c.541dupC (p.(Gln181Profs<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mi>\u2217<\/mml:mi><\/mml:math>20)) variant as the underlying genetic cause of the Chinese family with <jats:italic>NF1<\/jats:italic>. Moreover, our findings broaden the spectrum of <jats:italic>NF1<\/jats:italic> variants and provide molecular insights into the pathogenesis of <jats:italic>NF1<\/jats:italic>.<\/jats:p>","DOI":"10.1155\/2019\/2721357","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T18:30:46Z","timestamp":1575916246000},"page":"1-6","source":"Crossref","is-referenced-by-count":2,"title":["Identification of a Novel <i>NF1<\/i> Frameshift Variant in a Chinese Family with Neurofibromatosis Type 1"],"prefix":"10.1155","volume":"2019","author":[{"given":"Guoyao","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Cellular Biology and Genetics, Hunan Provincial Key Laboratory of Dong Medicine, Hunan University of Medicine, Huaihua, Hunan Province, China"},{"name":"Department of Neurology, The First Affiliated Hospital, Hunan University of Medicine, Huaihua, Hunan Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Hunan University of Medicine, Huaihua, Hunan Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youya","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Genetics, Hunan Provincial Key Laboratory of Dong Medicine, Hunan University of Medicine, Huaihua, Hunan Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueshuang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Genetics, Hunan Provincial Key Laboratory of Dong Medicine, Hunan University of Medicine, Huaihua, Hunan Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanchun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital, Hunan University of Medicine, Huaihua, Hunan Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Genyun","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Genetics, Hunan Provincial Key Laboratory of Dong Medicine, Hunan University of Medicine, Huaihua, Hunan Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sha","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital, Hunan University of Medicine, Huaihua, Hunan Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital, Hunan University of Medicine, Huaihua, Hunan Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9081-9797","authenticated-orcid":true,"given":"Haiou","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Genetics, Hunan Provincial Key Laboratory of Dong Medicine, Hunan University of Medicine, Huaihua, Hunan Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spen.2015.10.007"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2014.1756"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.4238\/2014.july.24.19"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2109"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1038\/srep11291"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.3390\/genes9040216"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0511-3"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90149-9"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3911"},{"key":"10","first-page":"19","volume-title":"The structure and function of the NF1 gene: molecular 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