McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830001, China.
Front Med. 2022 Oct;16(5):808-814. doi: 10.1007/s11684-021-0878-x. Epub 2022 Mar 21.
Epidermolysis bullosa (EB) is a group of clinically and genetically heterogeneous diseases characterized by trauma-induced mucocutaneous fragility and blister formation. Here, we investigated five Chinese families with EB, and eight variants including a novel nonsense variant (c.47G>A, p.W16*) in LAMA3, a known recurrent variant (c.74C>T, p.P25L) in KRT5, 2 novel (c.2531T>A, p.V844E; c.6811_6814del, p.R2271fs) and 4 known (c.6187C>T, p.R2063W; c.7097G>A, p.G2366D; c.8569G>T, p.E2857*; c.3625_3635del, p.S1209fs) variants in COL7A1 were detected. Notably, this study identified a nonsense variant in LAMA3 that causes EB within the Chinese population and revealed that this variant resulted in a reduction in LAMA3 mRNA and protein expression levels by nonsense-mediated mRNA decay. Our study expands the mutation spectra of Chinese patients with EB.
大疱性表皮松解症（EB）是一组临床和遗传异质性疾病，其特征是创伤诱导的黏膜皮肤脆弱性和水疱形成。在这里，我们研究了五个中国 EB 家系，并发现了包括 LAMA3 中的一个新的无义变异（c.47G>A，p.W16*）、KRT5 中的一个已知反复变异（c.74C>T，p.P25L）在内的 8 种变异，以及 2 种新的（c.2531T>A，p.V844E；c.6811_6814del，p.R2271fs）和 4 种已知的（c.6187C>T，p.R2063W；c.7097G>A，p.G2366D；c.8569G>T，p.E2857*；c.3625_3635del，p.S1209fs）COL7A1 变异。值得注意的是，本研究在中国人中发现了 LAMA3 中的一个无义变异导致 EB，并揭示了该变异通过无义介导的 mRNA 降解导致 LAMA3 mRNA 和蛋白表达水平降低。我们的研究扩展了中国 EB 患者的突变谱。
