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Two causes have been identified: some patients have an autosomal recessive disorder resulting from mutations in the FOLR1 gene, which encodes folate receptor alpha (52

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A significant negative latitude-dependent relationship was detected for carriage of the T allele, with occurrence of the cSHMT-C1420T polymorphic allele decreasing with increase in latitude ( r 2 =0.73, p 3R frequency in reported African and Eurasia studies found a significant negative relationship between latitude and frequency of the 3R allele ( r 2 =0.12, p =0.039) (Fig