title: Rapid detection of gene mutations responsible for non-syndromic aortic aneurysm and dissection using two different methods: resequencing microarray technology and next-generation sequencing.
abstract: Aortic aneurysm and/or dissection (AAD) is a life-threatening condition, and several syndromes are known to be related to AAD. In this study, two new technologies, resequencing array technology (ResAT) and next-generation sequencing (NGS), were used to analyze eight genes associated with syndromic AAD in 70 patients with non-syndromic AAD. Eighteen sequence variants were detected using both ResAT and NGS. In addition one of these sequence variants was detected by ResAT only and two additional variants by NGS only. Three of the 18 variants are likely to be pathogenic (in 4.3% of AAD patients and in 8.6% of a subset of patients with thoracic AAD), highlighting the importance of genetic analysis in non-syndromic AAD. ResAT and NGS similarly detected most, but not all, of the variants. Resequencing array technology was a rapid and efficient method for detecting most nucleotide substitutions, but was unable to detect short insertions/deletions, and it is impractical to update custom arrays frequently. Next-generation sequencing was able to detect almost all types of mutation, but requires improved informatics methods.
authors: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan.
authors: Haruya
authors: H
authors: Sakai
authors: Shinichi
authors: S
authors: Suzuki
authors: Takeshi
authors: T
authors: Mizuguchi
authors: Kiyotaka
authors: K
authors: Imoto
authors: Yuki
authors: Y
authors: Yamashita
authors: Hiroshi
authors: H
authors: Doi
authors: Masakazu
authors: M
authors: Kikuchi
authors: Yoshinori
authors: Y
authors: Tsurusaki
authors: Hirotomo
authors: H
authors: Saitsu
authors: Noriko
authors: N
authors: Miyake
authors: Munetaka
authors: M
authors: Masuda
authors: Naomichi
authors: N
authors: Matsumoto
mesh_terms: D000199:Actins / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000784:Aortic Dissection / Q000235:genetics*; D001014:Aortic Aneurysm / Q000235:genetics*; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D005260:Female; D000071837:Fibrillins; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D006801:Humans; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D008840:Microfilament Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA / Q000379:methods*; D017386:Sequence Homology, Amino Acid
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; C439971:COL3A1 protein, human; D024061:Collagen Type III; D000071837:Fibrillins; D051246:Glucose Transport Proteins, Facilitative; C509903:MYH11 protein, human; D008840:Microfilament Proteins; D018125:Receptors, Transforming Growth Factor beta; C430746:SLC2A10 protein, human; C572044:PLOD1 protein, human; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018995:Myosin Heavy Chains