The spectrum of mutations, including four novel ones, in the thiamine-responsive megaloblastic anemia geneSLC19A2 of eight families

Raz, Tal; Labay, Valentina; Baron, Dana; Szargel, Raymonde; Anbinder, Yefim; Barrett, Timothy; Rabl, Wolfgang; Viana, Marcos Borato; Mandel, Hanna; Baruchel, André; Cayuela, Jean‐Michel; Cohen, Nadine

doi:10.1002/1098-1004(200007)16:1<37::aid-humu7>3.0.co;2-9

Cited by 54 publications

(41 citation statements)

References 18 publications

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“…In 1978, a second case was reported by Viana & Carvalho (7). Since then, a number of cases have been described (4,(8)(9)(10)(11)(12)(13). It was postulated that this syndrome is related to defects in thiamine metabolism (1,7,14).…”

Section: Discussionmentioning

confidence: 99%

“…It is inherited in an autosomal recessive pattern. Unlike the familiar forms of diabetes in which polygenetic and environmental factors interact, diabetes in TRMA syndrome is a monogenic form of diabetes secondary to mutations in the SLC19A2 gene, which encodes a plasma membrane thiamine transporter, called THTR1 (2)(3)(4)(5)(6). The latter is a member of the solute carrier family that includes its homolog THTR2 and the reduced folate carrier.…”

Section: Introductionmentioning

confidence: 99%

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Thiamine transporter mutation: an example of monogenic diabetes mellitus

Alzahrani

Baitei²,

Zou³

et al. 2006

eur j endocrinol

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Objective: Thiamine-responsive megaloblastic anemia (TRMA) is a rare syndrome characterized by diabetes mellitus (DM), anemia, and sensorineural deafness. We describe the clinical course and the molecular defect of a young woman who was diagnosed to have this syndrome. Case: The patient is an 18-year-old girl who was born to non-consanguous parents. She was noted to be deafmute in the first year of life. She was diagnosed with DM at the age of 9 months and with severe anemia at the age of 2 years. An extensive work up could not identify the cause. She was treated with blood transfusions every 3-4 weeks for the past 16 years. A diagnosis of TRMA was suspected and the patient was treated with thiamine hydrochloride. Hemoglobin and platelets increased to normal values after a few weeks of thiamine therapy. Diabetic control significantly improved but she had no noticeable changes in the deafness. Methods: Peripheral blood DNAwas extracted from the patient, her mother, aunt, and a healthy sister. Exons and exon-intron boundaries of the thiamine transporter gene SLC19A2 were PCR amplified and directly sequenced. Results: A G515C homozygous mutation was identified in the SLC19A2 gene of the patient. This mutation changes Gly to Arg at codon 172 (G172R). The mother, an aunt, and a sister had a heterozygous G172R mutation. Conclusions: Mutations in thiamine transporter gene, SLC19A2, causes a rare form of monogenic diabetes, anemia, and sensorineural deafness. Thiamine induces a remarkable hematological response and improvement in the diabetic control but has no effect on deafness.European Journal of Endocrinology 155 787-792

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thiamine transporter mutation: an example of monogenic diabetes mellitus

Alzahrani

Baitei²,

Zou³

et al. 2006

eur j endocrinol

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“…It is perhaps noteworthy that the autosomal recessive disorder Rogers syndrome, or thiamine responsive megaloblastic anemia, has been linked to mutations in the THTR1 gene (12,32,51). Rogers syndrome is characterized by the occurrence of megaloblastic anemia, diabetes mellitus, sensorineural deafness, and abnormalities of the retina and heart anomalies.…”

Section: Discussionmentioning

confidence: 99%

A Putative Thiamine Transport Protein Is a Receptor for Feline Leukemia Virus Subgroup A

Mendoza

Anderson

Overbaugh

2006

J Virol

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Feline leukemia virus (FeLV) is a horizontally transmitted virus that causes a variety of proliferative and immunosuppressive diseases in cats. There are four subgroups of FeLV, A, B, C, and T, each of which has a distinct receptor requirement. The receptors for all but the FeLV-A subgroup have been defined previously. Here, we report the identification of the cellular receptor for FeLV-A, which is the most transmissible form of FeLV. The receptor cDNA was isolated using a gene transfer approach, which involved introducing sequences from a feline cell line permissive to FeLV-A into a murine cell line that was not permissive. The feline cDNA identified by this method was approximately 3.5 kb, and included an open reading frame predicted to encode a protein of 490 amino acids. This feline cDNA conferred susceptibility to FeLV-A when reintroduced into nonpermissive cells, but it did not render these cells permissive to any other FeLV subgroup. Moreover, these cells specifically bound FeLV-A-pseudotyped virus particles, indicating that the cDNA encodes a binding receptor for FeLV-A. The feline cDNA shares ϳ93% amino acid sequence identity with the human thiamine transport protein 1 (THTR1). The human THTR1 receptor was also functional as a receptor for FeLV-A, albeit with reduced efficiency compared to the feline orthologue. On the basis of these data, which strongly suggest the feline protein is the orthologue of human THTR1, we have named the feline receptor feTHTR1. Identification of this receptor will allow more detailed studies of the early events in FeLV transmission and may provide insights into FeLV pathogenesis.

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“…The deletion of the gene has no effect on mice when supplemented with thiamine. Several mutations in the human slc19a2 gene have been identified that result in TRMA [19,25]. Patients with TRMA are effectively treated with thiamine supplementation [19].…”

Section: Slc19a2mentioning

confidence: 99%

SLC19: the folate/thiamine transporter family

Ganapathy

Smith

Prasad

2004

Pfl�gers Archiv European Journal of Physiology

153

121

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The SLC19 gene family of solute carriers is a family of three transporter proteins with significant structural similarity, transporting, however, substrates with different structure and ionic charge. The three members of this gene family are expressed ubiquitously and mediate the transport of two important water-soluble vitamins, folate and thiamine. The concentrative transport of substrates mediated by the members of this gene family is energized by transcellular H(+)/OH(-) gradient. SLC19A1 is expressed at highest levels in absorptive cells where it is located in a polarized manner either in the apical or basal membrane, depending on the cell type. It mediates the transport of reduced folate and its analogs, such as methotrexate, which are anionic at physiological pH. SLC19A2 is expressed ubiquitously and mediates the transport of thiamine, a cation at physiological pH. SLC19A3 is also widely expressed and is capable of transporting thiamine. This review summarizes the current knowledge on the structural, functional, molecular and physiological aspects of the SLC19 gene family.

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The spectrum of mutations, including four novel ones, in the thiamine-responsive megaloblastic anemia geneSLC19A2 of eight families

Cited by 54 publications

References 18 publications

Thiamine transporter mutation: an example of monogenic diabetes mellitus

Thiamine transporter mutation: an example of monogenic diabetes mellitus

A Putative Thiamine Transport Protein Is a Receptor for Feline Leukemia Virus Subgroup A

SLC19: the folate/thiamine transporter family

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