The functionally neutral N314D variation in the GALT gene is associated with Duarte galactosemia and is widespread among various worldwide populations.
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.
Six out of thirteen (46%) daughters and two mothers of the remaining seven daughters (29%) were carriers for the N314D mutation of GALT associated with the Duarte variant of galactosaemia as compared to 16 out of 113 general population controls (14%) who possessed at least one N314D allele.
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.
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.
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.