title: Identification of a missense mutation of COL3A1 in a Chinese family with atypical Ehlers-Danlos syndrome using targeted next-generation sequencing.
abstract: Aortopathy represents an important cause of mortality in industrialized countries, with a number of genes identified as predispose factors. It can be difficult to identify the genetic lesions underlying this disorder, particularly when the phenotype is atypical. The present study performed targeted next‑generation sequencing of 428 genes associated with cardiovascular diseases in a family with aortopathy, the proband of which presented with abdominal aortic aneurysm rupture only, with tissue fragility noted in surgery. After targeted capture, sequencing and bioinformatics analysis, a missense mutation, p.A1259T, was identified in the collagen type III α1 (COL3A1) gene and co‑segregated with the disease in the family. Crystal structure modeling revealed abnormal hydrogen bonds generated by the mutation, which likely affected the spatial structure of the procollagen C‑propeptide. Mutations in the procollagen C‑propeptide are rare and genotype‑phenotype correlation may explain the atypical manifestations of affected individuals. The results of the present study suggested that targeted gene capture combined with next‑generation sequencing can serve as a useful technique in the genetic diagnosis of aortopathy, particularly in the content of an atypical phenotype.
authors.affiliation: Department of Vascular Surgery, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Vascular Surgery, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Han
authors.affiliation: Department of Vascular Surgery, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Vascular Surgery, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ran
authors.affiliation: Department of Vascular Surgery, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Tong
authors.initials: T
authors.lastname: Qiao
authors.affiliation: Center for Translational Medicine, Nanjing University Medical School, Nanjing, Jiangsu 210093, P.R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Yi
authors.affiliation: Department of Vascular Surgery, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Changjian
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Vascular Surgery, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Liu
mesh_terms: D017544:Aortic Aneurysm, Abdominal / Q000150:complications / Q000235:genetics; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D024061:Collagen Type III / Q000737:chemistry / Q000235:genetics*; D004535:Ehlers-Danlos Syndrome / Q000150:complications / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008875:Middle Aged; D008958:Models, Molecular; D020125:Mutation, Missense; D010375:Pedigree; D011487:Protein Conformation
chemical_list: C439971:COL3A1 protein, human; D024061:Collagen Type III