Ga. Diaz et al., Mutations in a new gene encoding a thiamine transporter cause thiamine-responsive megaloblastic anaemia syndrome, NAT GENET, 22(3), 1999, pp. 309-312
Thiamine-responsive megaloblastic anaemia syndrome (TRMA; MIM 249270) is an
autosomal recessive disorder with features that include megaloblastic anae
mia, mild thrombocytopenia and leucopenia, sensorineural deafness and diabe
tes mellitus(1-3). Treatment with pharmacologic doses of thiamine ameliorat
es the megaloblastic anaemia and diabetes mellitus. A defect in the plasma
membrane transport of thiamine has been demonstrated in erythrocytes and cu
ltured skin fibroblasts from TRMA patients(4-6). The gene causing TRMA was
assigned to 1q23.2-q23.3 by linkage analysis(7). Here we report the cloning
of a new gene, SLC19A2, identified from high-throughput 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 transme
mbrane domains. We identified 2 frameshift mutations in exon 2, a 1-bp inse
rtion and a 2-bp deletion, among four Iranian families with TRMA. The seque
nce homology and predicted structure of SLC19A2, as well as its role in TRM
A, suggest that its gene product is a thiamine carrier, the first to be ide
ntified in complex eukaryotes.