engleski

The frequencies of various mutations in GALT gene in Croatian population

Galactosemia is an inborn error of metabolism in which galactose breakdown is impaired. The most common form is caused by deficient galactose-1-phosphate uridyl transferase (GALT) activity and exhibits a wide spectrum of symptoms, depending on the residual enzyme activity. Individuals homoallelic for Q188R and K285N mutations within the GALT gene develop a severe phenotype, named classical galactosemia, with complete loss of enzyme activity. A milder form of galactosemia, known as Duarte variant, is caused by a mutation N314D within the GALT gene. Along with the N314D mutation, Duarte variants of galactosemia depend on other genetic changes such as intronic sequence variation G1391A in intron V (IVS5-24G>A) (Duarte-2) or silent mutation L218L (Duarte-1 or Los Angeles variant). In Duarte-2 variant, homozygotes have approximately 50% and heterozygotes 75% residual GALT activity while Duarte-1 is characterized by increased GALT activity. Although heterozygotes for classical galactosemia are asymptomatic at birth and Duarte galactosemia appears to be quite benign, there are some indications that these disorders can increase the risk of developing certain diseases later in life. The aim of our study was to analyze a healthy Croatian population for the frequencies of Q188R, K285N, IVS5-24G>A and N314D mutations within GALT gene. DNA samples from 166 healthy individuals were analysed for all four mutations by polymerase chain reaction and digestion with restriction enzymes (PCR-RFLP). Allele frequencies for Q188R, K285N, IVS5-24G>A and N314D were found to be 0 %, 0%, 3.6 % and 6.6 %, respectively. 30.3% of Duarte-2 variant were found among the persons carrying IVS5-24G>A and/or N314D mutations. The obtained results show that N314 is the most frequent mutation among the healthy Croatian population. Our results correlate well with those reported for healthy Slovenian population.

galactosemia; mutations

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