The gene mutated in thiamine-responsive anaemia with diabetes and deafness (TRMA) encodes a functional thiamine transporter

Details

Serval ID
serval:BIB_C1D355F4BC65
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The gene mutated in thiamine-responsive anaemia with diabetes and deafness (TRMA) encodes a functional thiamine transporter
Journal
Nature Genetics
Author(s)
Fleming  J. C., Tartaglini  E., Steinkamp  M. P., Schorderet  D. F., Cohen  N., Neufeld  E. J.
ISSN
1061-4036 (Print)
Publication state
Published
Issued date
07/1999
Volume
22
Number
3
Pages
305-8
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jul
Abstract
Thiamine-responsive megaloblastic anaemia with diabetes and deafness (TRMA; MIM 249270) is an autosomal recessive disease thought to be due to a defect in thiamine (vitamin B1) transport. Pharmacological doses of thiamine correct the anaemia, and in some cases improve the diabetes, although progressive sensorineural deafness is irreversible. Previous studies localized the TRMA gene to a 4-cM region on chromosome 1q23.3 (ref. 5), and fine-mapping has recently narrowed that region further. We have previously demonstrated that fibroblasts from people with TRMA lack high-affinity thiamine transport. Expression of a gene encoding a known yeast thiamine transporter, THI10 (refs 8-10), in TRMA mutant cells prevents apoptotic cell death in thiamine-depleted medium. On the basis of these studies, we hypothesized that a defective thiamine transporter causes TRMA. We undertook a candidate gene approach to identify putative thiamine transporters in the 1q23.3 critical region. Here we present evidence that the gene SLC19A2 (for solute carrier family 19 (thiamine transporter), member 2) encodes the first known mammalian thiamine transporter, which we designate thiamine transporter-1 (THTR-1).
Keywords
Amino Acid Sequence Anemia, Megaloblastic/complications/drug therapy/*genetics Animals Base Sequence Carrier Proteins/*genetics Cell Line DNA Primers/genetics DNA, Complementary/genetics Deafness/complications/*genetics Diabetes Complications Diabetes Mellitus/*genetics Humans *Membrane Transport Proteins Molecular Sequence Data *Mutation RNA, Messenger/genetics/metabolism Sequence Homology, Amino Acid Syndrome Thiamine/*metabolism/therapeutic use
Pubmed
Web of science
Create date
28/01/2008 13:58
Last modification date
20/08/2019 16:36
Usage data