Whatley, Sharon D., Ducamp, Sarah, Gouya, Laurent, Grandchamp, Bernard, Beaumont, Carole, Badminton, Michael Norman, Elder, George H., Holme, S. Alexander, Anstey, Alexander Vincent ORCID: https://orcid.org/0000-0002-6345-4144, Parker, Michelle, Corrigall, Anne V., Meissner, Peter N., Hift, Richard J., Marsden, Joanne T., Ma, Yun, Mieli-Vergani, Giorgina, Deybach, Jean-Charles and Puy, Hervé 2008. C-Terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload. American Journal of Human Genetics 83 (3) , pp. 408-414. 10.1016/j.ajhg.2008.08.003 |
Abstract
All reported mutations in ALAS2, which encodes the rate-regulating enzyme of erythroid heme biosynthesis, cause X-linked sideroblastic anemia. We describe eight families with ALAS2 deletions, either c.1706-1709 delAGTG (p.E569GfsX24) or c.1699-1700 delAT (p.M567EfsX2), resulting in frameshifts that lead to replacement or deletion of the 19–20 C-terminal residues of the enzyme. Prokaryotic expression studies show that both mutations markedly increase ALAS2 activity. These gain-of-function mutations cause a previously unrecognized form of porphyria, X-linked dominant protoporphyria, characterized biochemically by a high proportion of zinc-protoporphyrin in erythrocytes, in which a mismatch between protoporphyrin production and the heme requirement of differentiating erythroid cells leads to overproduction of protoporphyrin in amounts sufficient to cause photosensitivity and liver disease.
Item Type: | Article |
---|---|
Date Type: | Publication |
Status: | Published |
Schools: | Medicine Sustainable Places Research Institute (PLACES) |
Subjects: | Q Science > QR Microbiology > QR180 Immunology R Medicine > R Medicine (General) |
Publisher: | Elsevier |
ISSN: | 0002-9297 |
Last Modified: | 06 May 2023 02:06 |
URI: | https://orca.cardiff.ac.uk/id/eprint/23722 |
Citation Data
Cited 205 times in Scopus. View in Scopus. Powered By Scopus® Data
Actions (repository staff only)
Edit Item |