Publication: Loss-of-function mutation in thiamine transporter 1 in a family with autosomal dominant diabetes
Issued Date
2019-01-01
Resource Type
ISSN
1939327X
00121797
00121797
Other identifier(s)
2-s2.0-85065113592
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Mahidol University
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SCOPUS
Bibliographic Citation
Diabetes. Vol.68, No.5 (2019), 1084-1093
Suggested Citation
Prapaporn Jungtrakoon, Jun Shirakawa, Patinut Buranasupkajorn, Manoj K. Gupta, Dario F. De Jesus, Marcus G. Pezzolesi, Aussara Panya, Timothy Hastings, Chutima Chanprasert, Christine Mendonca, Rohit N. Kulkarni, Alessandro Doria Loss-of-function mutation in thiamine transporter 1 in a family with autosomal dominant diabetes. Diabetes. Vol.68, No.5 (2019), 1084-1093. doi:10.2337/db17-0821 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/52369
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Title
Loss-of-function mutation in thiamine transporter 1 in a family with autosomal dominant diabetes
Abstract
© 2019 by the American Diabetes Association. Solute Carrier Family 19 Member 2 (SLC19A2) encodes thiamine transporter 1 (THTR1), which facilitates thiamine transport across the cell membrane. SLC19A2 homozygous mutations have been described as a cause of thiamine-responsive megaloblastic anemia (TRMA), an autosomal recessive syndrome characterized by megaloblastic anemia, diabetes, and sensorineural deafness. Here we describe a loss-of-function SLC19A2 mutation (c.A1063C: p.Lys355Gln) in a family with earlyonset diabetes and mild TRMA traits transmitted in an autosomal dominant fashion. We show that SLC19A2- deficient b-cells are characterized by impaired thiamine uptake, which is not rescued by overexpression of the p.Lys355Gln mutant protein. We further demonstrate that SLC19A2 deficit causes impaired insulin secretion in conjunction with mitochondrial dysfunction, loss of protection against oxidative stress, and cell cycle arrest. These findings link SLC19A2 mutations to autosomal dominant diabetes and suggest a role of SLC19A2 in b-cell function and survival.