title: Ehlers-Danlos syndrome type IV is associated with a novel G984R COL3A1 mutation.
abstract: Ehlers-Danlos syndrome type IV is an autosomal dominant connective tissue disease. Mutations in COL3A1 have been identified to underlie this disease; however, to the best of our knowledge, no COL3A1 mutations have been reported in Ehlers-Danlos syndrome type IV patients with an ascending aortic aneurysm. In order to develop further understanding of COL3A1 mutations, an Ehlers-Danlos syndrome type IV patient diagnosed with an ascending aortic aneurysm and a familial history of sudden mortality was analyzed. Genomic DNA was isolated from the peripheral blood of the patient and his family members. All coding exons of eight aneurysm-related genes (FBN1, TGFBR1, TGFBR 2, MYH11, ACTA2, SLC2A10, NOTCH1 and COL3A1) were amplified using polymerase chain reaction (PCR). The PCR products were sequenced with the ABI 3100 Genetic Analyzer, and a mutation was predicted and identified using Polyphen-2, SIFT and Mutation Taster. The novel mutation was identified as c.2950G>A in COL3A1, which results in p.G984R. All three programs predicted this mutation to be deleterous to the protein function. The novel mutation identified in this study is potentially responsible for Ehlers-Danlos syndrome type IV in this patient, and expands the spectrum of COL3A1 mutations.
authors.affiliation: Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Wei
authors.affiliation: Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Jinlan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001014:Aortic Aneurysm / Q000150:complications / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D024061:Collagen Type III / Q000235:genetics*; D003238:Connective Tissue / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D004535:Ehlers-Danlos Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016415:Sequence Alignment
chemical_list: C439971:COL3A1 protein, human; D024061:Collagen Type III