Comprehensive genetic screening for vascular Ehlers–Danlos syndrome through an amplification‐based next‐generation sequencing system. Issue 1 (3rd October 2022)

• Record Type: Journal Article
• Authors: Yamaguchi, Tomomi; Hayashi, Shujiro; Hayashi, Daisuke; Matsuyama, Takeshi; Koitabashi, Norimichi; Ogiwara, Kenichi; Noda, Masaaki; Nakada, Chiai; Fujiki, Shinya; Furutachi, Akira; Tanabe, Yasuhiko; Yamanaka, Michiko; Ishikawa, Aki; Mizukami, Miyako; Mizuguchi, Asako; Sugiura, Kazumitsu; Sumi, Makoto; Yamazawa, Hirokuni; Izawa, Atsushi; Wada, Yuko; Fujikawa, Tomomi; Takiguchi, Yuri; Wakui, Keiko; Takano, Kyoko; Nishio, Shin‐Ya; Kosho, Tomoki
• Is Part Of: American journal of medical genetics. Volume 191:Issue 1(2023)
• Page Start: 37
• Page End: 51
• Publication Date: 2022-10-03
• Subjects: amplification‐based next‐generation sequencing -- COL3A1 -- copy number variations -- formalin‐fixed and paraffin‐embedded (FFPE) samples -- hereditary connective tissue disorders (HCTDs) -- vascular Ehlers–Danlos syndrome (vEDS); Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.62982
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract: Vascular Ehlers–Danlos syndrome (vEDS) is a hereditary connective tissue disorder (HCTD) characterized by arterial dissection/aneurysm/rupture, sigmoid colon rupture, or uterine rupture. Diagnosis is confirmed by detecting heterozygous variants in COL3A1 . This is the largest Asian case series and the first to apply an amplification‐based next‐generation sequencing through custom panels of causative genes for HCTDs, including a specific method of evaluating copy number variations. Among 429 patients with suspected HCTDs analyzed, 101 were suspected to have vEDS, and 33 of them (32.4%) were found to have COL3A1 variants. Two patients with a clinical diagnosis of Loeys–Dietz syndrome and/or familial thoracic aortic aneurysm and dissection were also found to have COL3A1 variants. Twenty cases (57.1%) had missense variants leading to glycine (Gly) substitutions in the triple helical domain, one (2.9%) had a missense variant leading to non‐Gly substitution in this domain, eight (22.9%) had splice site alterations, three (8.6%) had nonsense variants, two (5.7%) had in‐frame deletions, and one (2.9%) had a multi‐exon deletion, including two deceased patients analyzed with formalin‐fixed and paraffin‐embedded samples. This is a clinically useful system to detect a wide spectrum of variants from various types of samples.