Refined mapping of the gene for thiamine-responsive megaloblastic anemia syndrome and evidence for genetic homogeneity

Tal Raz, Tim Barrett, Raymonde Szargel, Hanna Mandel, Ellis J. Neufeld, Kazuto Nosaka, Marcos B. Viana, Nadine Cohen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Thiamine-responsive megaloblastic anemia (TRMA, also known as Rogers syndrome, OMIM 249270) is a rare autosomal recessive disorder characterized by a triad of megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Patients respond, to varying degrees, to treatment with megadoses of thiamine. We have recently shown genetic linkage of the TRMA gene to a 16-centimorgan (cM) region on 1q23.2-1q23.3 based on the analysis of four large, inbred families of Alaskan, Italian, and Israeli-Arab origin. Here we narrow the TRMA interval down to 4 cM based on genetic recombination, homozygosity mapping, and linkage disequilibrium (highest LOD score of 12.5 at D1S2799, at a recombination fraction of 0). We provide further evidence that the TRMA gene is located in this region and confirm the homogeneity of the disease. In this analysis, we genotyped seven additional families of diverse ethnic origin (Pakistani, Indian, Italian, Brazilian, and Japanese), and analyzed additional markers in two previously reported families showing evidence of linkage disequilibrium in a large area of their haplotypes. The multi-system manifestations of TRMA suggest that thiamine has a pivotal role in a multiplicity of physiological processes. Mapping the TRMA gene and understanding the molecular basis of the disease might, thus, shed light on the role of thiamine in common disorders such as deafness, anemia, and diabetes.

Original languageAmerican English
Pages (from-to)455-461
Number of pages7
JournalHuman Genetics
Issue number4
StatePublished - 1998
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements This work was supported by the Juvenile Diabetes Foundation International (to N.C.), and in part by the Ministry of Sciences and Arts (Israel) (to N.C.) and by the Joseph Alias Fund for Medical Research (to H.M.). We are grateful to Professor Borgna-Pignatti for supplying us with samples from kindred 2. The collaboration of the families is gratefully acknowledged.


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