The functionally neutral N314D variation in the GALT gene is associated with Duarte galactosemia and is widespread among various worldwide populations.
Two unusual genotypes were observed in 2 patients homozygous for the Duarte-2 N314D allele and heterozygous for a novel mutation (Q207X- N314D/N314D in a classic galactosemia and T23A- N314D/N314D in a Duarte-2 case).
In summary, galactosemia is a heterogeneous disorder at the molecular level, and mutation N314D, appears to be an ancient genetic variant of the GALT gene.Hum Mutat 15:206, 2000.
We conclude that the codon change N314D in cis with the base-pair transition 1721C-->T produces the LA variant of galactosemia and that this nucleotide change increases GALT activity by increasing GALT protein abundance without increasing transcription or decreasing thermal lability.
We screened a large population for the Q188R and N314D sequence changes to investigate the prevalence of Q188R in G/G galactosemia, the effect of homozygosity for Q188R on outcome, and the prevalence and biochemical phenotype of the N314D sequence change.
Our limited data set on galactosemia mutations in Japanese suggests that the N314D GALT mutation encoding the Duarte variant arose before Asian and Caucasian people diverged and that classic galactosemia mutations arose and/or accumulated after the divergence of Asian and Caucasian populations.
Possession of GALT polymorphisms previously linked with low GALT activity, including the Q188R mutation of classic galactosemia or N314D mutation of the Duarte galactosemia variant, was associated with significantly higher FSH, even in the heterozygous state.