PMID- 10391223
OWN - NLM
STAT- MEDLINE
DCOM- 19990719
LR  - 20131121
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 22
IP  - 3
DP  - 1999 Jul
TI  - Mutations in a new gene encoding a thiamine transporter cause thiamine-responsive
      megaloblastic anaemia syndrome.
PG  - 309-12
AB  - Thiamine-responsive megaloblastic anaemia syndrome (TRMA; MIM 249270) is an
      autosomal recessive disorder with features that include megaloblastic anaemia,
      mild thrombocytopenia and leucopenia, sensorineural deafness and diabetes
      mellitus. Treatment with pharmacologic doses of thiamine ameliorates the
      megaloblastic anaemia and diabetes mellitus. A defect in the plasma membrane
      transport of thiamine has been demonstrated in erythrocytes and cultured skin
      fibroblasts from TRMA patients. The gene causing TRMA was assigned to
      1q23.2-q23.3 by linkage analysis. Here we report the cloning of a new gene,
      SLC19A2, identified from high-through-put genomic sequences due to homology with 
      SLC19A1, encoding reduced folate carrier 1 (refs 8-10). We cloned the entire
      coding region by screening a human fetal brain cDNA library. SLC19A2 encodes a
      protein (of 497 aa) predicted to have 12 transmembrane domains. We identified 2
      frameshift mutations in exon 2. a 1-bp insertion and a 2-bp deletion, among four 
      Iranian families with TRMA. The sequence homology and predicted structure of
      SLC19A2, as well as its role in TRMA, suggest that its gene product is a thiamine
      carrier, the first to be identified in complex eukaryotes.
FAU - Diaz, G A
AU  - Diaz GA
AD  - Department of Human Genetics, Mount Sinai School of Medicine, New York, New York,
      USA.
FAU - Banikazemi, M
AU  - Banikazemi M
FAU - Oishi, K
AU  - Oishi K
FAU - Desnick, R J
AU  - Desnick RJ
FAU - Gelb, B D
AU  - Gelb BD
LA  - eng
SI  - GENBANK/AF153330
GR  - 5 P30 HD 28822/HD/NICHD NIH HHS/United States
GR  - P01-HD28822/HD/NICHD NIH HHS/United States
PT  - Journal Article
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, Complementary)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (SLC19A2 protein, human)
RN  - X66NSO3N35 (Thiamine)
SB  - IM
MH  - Amino Acid Sequence
MH  - Anemia, Megaloblastic/complications/drug therapy/*genetics
MH  - Base Sequence
MH  - Carrier Proteins/*genetics
MH  - Cloning, Molecular
MH  - DNA, Complementary/genetics
MH  - Deafness/complications/genetics
MH  - Diabetes Complications
MH  - Diabetes Mellitus/genetics
MH  - Female
MH  - Humans
MH  - Male
MH  - *Membrane Transport Proteins
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Pedigree
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 - 10.1038/10385 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Jul;22(3):309-12. doi: 10.1038/10385.