TY - JOUR
T1 - Comprehensive genetic screening for vascular Ehlers–Danlos syndrome through an amplification-based next-generation sequencing system
AU - Yamaguchi, Tomomi
AU - Hayashi, Shujiro
AU - Hayashi, Daisuke
AU - Matsuyama, Takeshi
AU - Koitabashi, Norimichi
AU - Ogiwara, Kenichi
AU - Noda, Masaaki
AU - Nakada, Chiai
AU - Fujiki, Shinya
AU - Furutachi, Akira
AU - Tanabe, Yasuhiko
AU - Yamanaka, Michiko
AU - Ishikawa, Aki
AU - Mizukami, Miyako
AU - Mizuguchi, Asako
AU - Sugiura, Kazumitsu
AU - Sumi, Makoto
AU - Yamazawa, Hirokuni
AU - Izawa, Atsushi
AU - Wada, Yuko
AU - Fujikawa, Tomomi
AU - Takiguchi, Yuri
AU - Wakui, Keiko
AU - Takano, Kyoko
AU - Nishio, Shin Ya
AU - Kosho, Tomoki
N1 - Publisher Copyright:
© 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
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U2 - 10.1002/ajmg.a.62982
DO - 10.1002/ajmg.a.62982
M3 - Article
AN - SCOPUS:85139180988
SN - 1552-4825
VL - 191
SP - 37
EP - 51
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 1
ER -