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

Nat Genet. 1999 Jul;22(3):305-8. doi: 10.1038/10379.

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).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Anemia, Megaloblastic / complications
  • Anemia, Megaloblastic / drug therapy
  • Anemia, Megaloblastic / genetics*
  • Animals
  • Base Sequence
  • Carrier Proteins / genetics*
  • Cell Line
  • DNA Primers / genetics
  • DNA, Complementary / genetics
  • Deafness / complications
  • Deafness / genetics*
  • Diabetes Complications
  • Diabetes Mellitus / genetics*
  • Humans
  • Membrane Transport Proteins*
  • Molecular Sequence Data
  • Mutation*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Homology, Amino Acid
  • Syndrome
  • Thiamine / metabolism*
  • Thiamine / therapeutic use

Substances

  • Carrier Proteins
  • DNA Primers
  • DNA, Complementary
  • Membrane Transport Proteins
  • RNA, Messenger
  • SLC19A2 protein, human
  • Thiamine

Associated data

  • GENBANK/AF135488
  • GENBANK/AF158233
  • GENBANK/AF160186
  • GENBANK/AF160756