Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026
Functional characterization of a novel ZIP8 variant causing impaired manganese homeostasis and congenital disorders of glycosylation.
СтатьяКлинический случайНазвание и аннотация: Перевод в очереди
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Fujishiro Hitomi, Morisada Naoya, Mitani Nao, Nakayama Rina, Goto Natsuki, Nishito Yukina, Kambe Taiho, Okamoto Nobuhiko, Wada Yoshinao, Ishida Yusuke, Suzuki Hisato, Nozu Kandai, Kosaki Kenjiro, Himeno Seiichiro, Sumi Daigo
Аннотация
ZIP8, encoded by SLC39A8, mediates cellular uptake of divalent metal ions, including manganese (Mn). Mutations in SLC39A8 cause a congenital disorder of glycosylation (CDG) associated with Mn deficiency (SLC39A8-CDG). Here, we report a novel case of SLC39A8-CDG harboring a previously unreported mutation (p.F206I) in the transmembrane domain 3 (TMD3). The patient showed markedly low serum Mn levels and abnormal glycosylation. To evaluate the functional consequences of this variant, we generated cells expressing hZIP8-F206I. Mn, cadmium, and zinc uptake levels in cells expressing hZIP8-F206I were approximately half of those in cells expressing wild-type hZIP8. The mutant hZIP8 also showed reduced plasma membrane localization. These findings suggest that this previously unreported mutation in TMD3 significantly impairs ZIP8-mediated metal transport, leading to CDG.