The spectrum of mutations, including four novel ones, in the thiamine-responsive megaloblastic anemia gene SLC19A2 of eight families

Thiamine responsive megaloblastic anemia (TRMA) is an autosomal recessive d isorder with a triad of symptoms: megaloblastic anemia, deafness, and non-t ype 1 diabetes mellitus. Occasionally, cardiac abnormalities and abnormalit ies of the optic nerve and retina occur as well. Patients with TRMA often r espond to treatment with pharmacological doses of thiamine. Recently, mutat ions were found in patients with TRMA in a thiamine transporter gene (SLC19 A2). We here describe the mutations found in eight additional families, We found four novel mutations and three that were previously described. Of the novel ones, one is a nonsense mutation in exon 1 (E65X), two are missense mutations in exon 2 (S142E D93H)1 and another is a mutation in the splicing donor site at the 5' end of intron 4 (C1223+1G>A). We also summarize the s tate of knowledge on all mutations found to date in TRMA patients. SLC19A2 is the first thiamine transporter gene to be described in humans. Reviewing the location and effect of the disease causing mutations can shed light on the way the protein functions and suggest ways to continue its investigati on. Hum Mutat 16:37-43, 2000. (C) 2000 Wiley-Liss, Inc.