Novel variants in LAMA3 and COL7A1 and recurrent variant in KRT5 underlying epidermolysis bullosa in five Chinese families

Abstract

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.

Keywords

epidermolysis bullosa / LAMA3 / COL7A1 / KRT5 / Chinese families

References

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Acknowledgements

We are grateful to the patients and their family members for their participation. This work was financially supported by the National Natural Science Foundation of China (No. 81788101), the National Key Research and Development Program of China (No. 2016YFC0905100), the CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2016-I2M-1-002), and the Natural Science Foundation of Beijing (No. 7172167).

Compliance with ethics guidelines

Rongrong Wang, Liwei Sun, Xiaerbati Habulieti, Jiawei Liu, Kexin Guo, Xueting Yang, Donglai Ma, and Xue Zhang declare that they have no conflict of interest. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/ 10.1007/s11684-021-0878-x and is accessible for authorized users.

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