The biological significance of somatic mutations in rare genetic liver diseases has remained elusive. A study using genomic sequencing paired with experimental cell-based assays has shed light on the selective advantage and accumulation of somatic variants in SERPINA1 found in liver explants from patients with alpha-1 anti-trypsin deficiency.
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Fig. 1: Somatic variants in SERPINA1 can reduce the accumulation of disease-associated A1AT.
References
Vento, S. & Cainelli, F. Lancet Glob. Health 10, e471–e472 (2022).
ArticleCASPubMedGoogle Scholar
Devarbhavi, H. et al. J. Hepatol. 79, 516–537 (2023).
ArticlePubMedGoogle Scholar
Brzozowska, N. et al. Nat. Genet.https://doi.org/10.1038/s41588-025-02125-1 (2025).
ArticlePubMedGoogle Scholar
Zhu, M. et al. Cell 177, 608–621.e12 (2019).
ArticleCASPubMedPubMed CentralGoogle Scholar
Ng, S. W. K. et al. Nature 598, 473–478 (2021).
ArticleCASPubMedGoogle Scholar
Wang, Z. et al. Cell 186, 1968–1984.e20 (2023).
ArticleCASPubMedPubMed CentralGoogle Scholar
Demers, S. I., Russo, P., Lettre, F. & Tanguay, R. M. Hum. Pathol. 34, 1313–1320 (2003).
ArticleCASPubMedGoogle Scholar
Kvittingen, E. A., Rootwelt, H., Berger, R. & Brandtzaeg, P. J. Clin. Invest. 94, 1657–1661 (1994).
ArticleCASPubMedPubMed CentralGoogle Scholar
Saito, K. et al. Am. J. Med. Genet. 56, 80–86 (1995).
ArticleCASPubMedGoogle Scholar
Uchino, M. et al. Acta Neuropathol. 90, 203–207 (1995).
ArticleCASPubMedGoogle Scholar
Hirschhorn, R. et al. Nat. Genet. 13, 290–295 (1996).
ArticleCASPubMedGoogle Scholar
McDermott, D. H. et al. Cell 160, 686–699 (2015).
ArticleCASPubMedPubMed CentralGoogle Scholar
Hakim, A. et al. J. Hepatol. 70, 1214–1221 (2019).
ArticleCASPubMedPubMed CentralGoogle Scholar
Zheng, M. et al. EBioMedicine 95, 104747 (2023).
ArticleCASPubMedPubMed CentralGoogle Scholar
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Acknowledgements
S.V. is supported by NIH/NIDDK, R01 DK131033.
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Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
Sílvia Vilarinho
Department of Genetics, Yale School of Medicine, New Haven, CT, USA
Sílvia Vilarinho
Department of Pathology, Yale School of Medicine, New Haven, CT, USA
Sílvia Vilarinho
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Sílvia Vilarinho
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Vilarinho, S. The interplay between germline and somatic variants in alpha-1 anti-trypsin deficiency liver disease. Nat Genet (2025). https://doi.org/10.1038/s41588-025-02151-z
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Published:01 April 2025
DOI:https://doi.org/10.1038/s41588-025-02151-z
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