title: Mutations in MCT1 cDNA in patients with symptomatic deficiency in lactate transport.
abstract: We identified 5 patients with subnormal erythrocyte lactate transport plus symptoms and signs of muscle injury on exercise and heat exposure. All had transport rates below the 95% envelope for normals. Three cases had rates 40-50% of mean normal. One was found to have a missense mutation in monocarboxylate transporter 1 (MCT1), the gene for the red cell lactate transporter (also expressed in skeletal muscle), at a conserved site, which was not mutated in a cohort of 90 normal humans. The other 2 cases had a different missense mutation (at a nonconserved site), which was also not mutated in the normal cohort. All 3 patients were heterozygotes. We presume that these mutations are responsible for their subnormal lactate transport, and hence their muscle injury under environmental stress; homozygous patients should be more seriously compromised. The other 2 cases had lactate transport rates 60-65% of mean normal, and their MCT1 revealed a third mutation, which proved to be a common polymorphism in the normal cohort. These 2 patients may be physiologic outliers in lactate transport, with their muscle damage arising from some other genetic defect.
authors.affiliation: Biochemical Pathology Division, Environmental Pathology Department, Room M093C, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
authors.forename: N
authors.initials: N
authors.lastname: Merezhinskaya
authors.forename: W N
authors.initials: WN
authors.lastname: Fishbein
authors.forename: J I
authors.initials: JI
authors.lastname: Davis
authors.forename: J W
authors.initials: JW
authors.lastname: Foellmer
mesh_terms: D000328:Adult; D001132:Arm / Q000098:blood supply; D001693:Biological Transport, Active / Q000235:genetics; D002239:Carbohydrate Metabolism, Inborn Errors / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics*; D004587:Electrophoresis, Agar Gel; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters; D018482:Muscle, Skeletal / Q000737:chemistry; D009154:Mutation / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012039:Regional Blood Flow / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D027501:Monocarboxylic Acid Transporters; D012333:RNA, Messenger; D019344:Lactic Acid