Abstract
We have previously reported two novel mutations in the 5′-untranslated region (UTR) of the gene for folate receptor-α (FOLR1). In our search for additional mutations, 92 patient samples with elevated levels of homocysteine were screened by single-strand conformation polymorphism (SSCP) between nt −425 and −782, and −712 and −1110. Between nt −425 and −782 we did not find any mutations. Between nt −712 and −1110 there were three novel mutations. One subject had two mutations very close to each other, c.−856C>T and c.−921T>C. Two subjects had a c.−1043G>A mutation. To get an idea of the prevalence of FOLR1 mutations in an unselected population, we also screened 692 healthy school children for mutations. In this cohort, between nt −188 and +272 we discovered one novel mutation, a single nucleotide substitution, c.−18C>T, in addition to five children with the 25-bp deletion mutation previously described by us. Thus, so far we have discovered six novel mutations in the 5′-UTR region of the gene for folate receptor-α. We genotyped all 17 subjects with a FOLR1 mutation for the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism, and developed new single-nucleotide polymorphism (SNP) genotyping protocols for MTHFR 1298A>C and 1793G>A utilising Pyrosequencing™ technology. None of the 17 subjects had the 677TT genotype, which ruled out this as a cause of elevated homocysteine levels, which was observed in some of the subjects. Further studies of mutations in the 5′-UTR of FOLR1, and in particular of their interplay with folate intake status, are warranted.
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