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The spectrum of mutations, including four novel ones, in the thiamine‐responsive megaloblastic anemia gene SLC19A2 of eight families
Author(s) -
Raz Tal,
Labay Valentina,
Baron Dana,
Szargel Raymonde,
Anbinder Yefim,
Barrett Tim,
Rabl Wolfgang,
Viana Marcos B.,
Mandel Hanna,
Baruchel Andre,
Cayuela JeanMichel,
Cohen Nadine
Publication year - 2000
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/1098-1004(200007)16:1<37::aid-humu7>3.0.co;2-9
Subject(s) - megaloblastic anemia , biology , thiamine , exon , missense mutation , genetics , mutation , anemia , intron , nonsense mutation , gene , medicine , endocrinology , vitamin b12 , biochemistry
Thiamine responsive megaloblastic anemia (TRMA) is an autosomal recessive disorder with a triad of symptoms: megaloblastic anemia, deafness, and non‐type 1 diabetes mellitus. Occasionally, cardiac abnormalities and abnormalities of the optic nerve and retina occur as well. Patients with TRMA often respond to treatment with pharmacological doses of thiamine. Recently, mutations were found in patients with TRMA in a thiamine transporter gene ( SLC19A2 ). 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 (S142F, D93H), and another is a mutation in the splicing donor site at the 5′ end of intron 4 (C1223+1G>A). We also summarize the state 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 investigation. Hum Mutat 16:37–42, 2000. © 2000 Wiley‐Liss, Inc.