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Recent GWAS study suggested common variant(s) in <jats:italic>FBN1<\/jats:italic> is associated with STAAD. The present study aims to test this hypothesis and to identify mutation spectrum by targeted exome sequencing of the <jats:italic>FBN1<\/jats:italic> gene in 146 unrelated patients with STAAD. Totally, 15.75% of <jats:italic>FBN1<\/jats:italic> variants in STAAD were identified, including 5 disruptive and 18 missense mutations. Most of the variants were novel. Genotype-phenotype correlation analysis suggested that the maximum aortic diameter in the disruptive mutation group was significantly larger than that in the non-Cys missense mutation group. Interestingly, the variant Ala27Thr at \u22121 position, which is predicted to change the cleavage site of the signal peptidase of fibrillin-1, was detected in two unrelated patients. Furthermore, genotyping analysis of this variant detected 10 heterozygous Ala27Thr from additional 666 unrelated patients (1.50%), versus 7 from 1500 controls (0.47%), indicating a significant association of this variant with STAAD. Collectively, the identification of the variant Ala27Thr may represent a relatively common genetic predisposition and a novel pathogenetic mechanism for STAAD. Also, expansion of the mutation spectrum in <jats:italic>FBN1<\/jats:italic> will be helpful in genetic counselling for Chinese patients with STAAD.<\/jats:p>","DOI":"10.1038\/srep13115","type":"journal-article","created":{"date-parts":[[2015,8,14]],"date-time":"2015-08-14T09:16:44Z","timestamp":1439543804000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Wide mutation spectrum and frequent variant Ala27Thr of FBN1 identified in a large cohort of Chinese patients with sporadic TAAD"],"prefix":"10.1038","volume":"5","author":[{"given":"Jun","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lun","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lixin","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Xi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuxia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunmei","family":"Piao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongsheng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,8,14]]},"reference":[{"key":"BFsrep13115_CR1","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1038\/nature10145","volume":"473","author":"ME Lindsay","year":"2011","unstructured":"Lindsay, M. 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