PMID- 10391222
OWN - NLM
STAT- MEDLINE
DCOM- 19990719
LR  - 20131121
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 22
IP  - 3
DP  - 1999 Jul
TI  - The gene mutated in thiamine-responsive anaemia with diabetes and deafness (TRMA)
      encodes a functional thiamine transporter.
PG  - 305-8
AB  - 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).
FAU - Fleming, J C
AU  - Fleming JC
AD  - Division of Hematology, Children's Hospital, Dana Farber Cancer Institute, and
      Harvard Medical School, Boston, Massachusetts 02115, USA.
FAU - Tartaglini, E
AU  - Tartaglini E
FAU - Steinkamp, M P
AU  - Steinkamp MP
FAU - Schorderet, D F
AU  - Schorderet DF
FAU - Cohen, N
AU  - Cohen N
FAU - Neufeld, E J
AU  - Neufeld EJ
LA  - eng
SI  - GENBANK/AF135488
SI  - GENBANK/AF158233
SI  - GENBANK/AF160186
SI  - GENBANK/AF160756
GR  - T32 HL07574/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Complementary)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (SLC19A2 protein, human)
RN  - X66NSO3N35 (Thiamine)
SB  - IM
MH  - Amino Acid Sequence
MH  - Anemia, Megaloblastic/complications/drug therapy/*genetics
MH  - Animals
MH  - Base Sequence
MH  - Carrier Proteins/*genetics
MH  - Cell Line
MH  - DNA Primers/genetics
MH  - DNA, Complementary/genetics
MH  - Deafness/complications/*genetics
MH  - Diabetes Complications
MH  - Diabetes Mellitus/*genetics
MH  - Humans
MH  - *Membrane Transport Proteins
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - RNA, Messenger/genetics/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Syndrome
MH  - Thiamine/*metabolism/therapeutic use
EDAT- 1999/07/03 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/07/03 10:00
PHST- 1999/07/03 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/07/03 10:00 [entrez]
AID - 10.1038/10379 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Jul;22(3):305-8. doi: 10.1038/10379.