Novel mutations in the 5'-UTR of the FOLR1 gene.
We have previously reported two novel mutations in the 5'-untranslated region (UTR) of the gene for folate receptor-alpha (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-alpha. 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.
Department of Clinical Chemistry, Orebro University Hospital, Orebro, Sweden. anna.borjel@orebroll.se
Anna K
AK
Börjel
Agneta
A
Yngve
Michael
M
Sjöström
Torbjörn K
TK
Nilsson
D020121:5' Untranslated Regions / Q000235:genetics*; D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D005260:Female; D058975:Folate Receptor 1; D058973:Folate Receptors, GPI-Anchored; D005820:Genetic Testing; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011956:Receptors, Cell Surface / Q000235:genetics*
D020121:5' Untranslated Regions; D002352:Carrier Proteins; C548696:FOLR1 protein, human; D058975:Folate Receptor 1; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D006710:Homocysteine