59 research outputs found
Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia
Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism-dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates
Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia.
Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism-dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates.Action Medical ResearchThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1160
Ectopic pregnancy secondary to in vitro fertilisation-embryo transfer: pathogenic mechanisms and management strategies
M. Darder Lissòn: De nominibus equorum circensium. Pars occidentis. Pp. 402, 16 pls. Barcelona: Reial Acadèmia de Bones Lletres, 1996. Paper.
Leonis Baptistae Alberti Momus, ediderunt Paolo d'Alessandro e Francesco Furlan, e Nota al texto, por Paolo d'Alessandro y Francesco Furlan, in Leon Battista Alberti. Momo (Biblioteca de la Utopiá, 16)
Ricostruzione stemmatica dei testimoni del Momus di Leon Battista Alberti (2 idiografi, alcuni apografi, due edizioni a stampa, di cui una instar codicis) ed edizione critica del test
The role of Latin in the early modern world : linguistic identity and nationalism, 1350-1800
- …