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

Thiamine-responsive megaloblastic anaemia with diabetes and deafness(1) (TR MA; MIM 249270) is an autosomal recessive disease thought to be due to a de fect in thiamine (vitamin B1) transport(2,3). Pharmacological doses of thia mine correct the anaemia, and in some cases improve the diabetes, although progressive sensorineural deafness is irreversible(4). Previous studies loc alized the TRMA gene to a 4-cM region on chromosome 1q23.3 (ref. 5), and fi ne-mapping has recently narrowed that region further(6,7). We have previous ly demonstrated that fibroblasts from people with TRMA lack high-affinity t hiamine transports. Expression of a gene encoding a known yeast thiamine tr ansporter, THI10 (refs 8-10), in TRMA mutant cells prevents apoptotic cell death in thiamine-depleted medium. On the basis of these studies, we hypoth esized that a defective thiamine transporter causes TRMA. We undertook a ca ndidate gene approach to identify putative thiamine transporters in the 1q2 3.3 critical region. Here we present evidence that the gene SLC19A2 (for so lute carrier family 19 (thiamine transporter), member 2) encodes the first known mammalian thiamine transporter, which we designate thiamine transport er-1 (THTR-1).