Mutations in MCT1 cDNA in patients with symptomatic deficiency in lactate transport

✍ Scribed by Natalya Merezhinskaya; William N. Fishbein; John I. Davis; John W. Foellmer

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 308 KB
• Volume: 23
• Category: Article
• ISSN: 0148-639X
• DOI: 10.1002/(sici)1097-4598(200001)23:1<90::aid-mus12>3.0.co;2-m

✦ Synopsis

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.