Low allelic heterogeneity in a sample of Mexican patients with classical galactosaemia

Abstract

Classical galactosaemia is an autosomal recessive disease of galactose metabolism caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT). Galactosaemia is not included in the neonatal screening programme in Mexico and it is necessary to implement methodologies for prompt diagnosis of these patients to establish treatment. To date, more than 190 mutations in the GALT gene have been reported, most in caucasian populations, but there have been no reports of mutations in Latin-American populations. We report here the mutational spectrum in 19 Mexican galactosaemic patients. The most frequent mutations were p.Q188R, p.N314D and IVS2-2A>G, which together represented 71% of detected mutations. The mutation IVS2-2A>G, which has been detected only in Hispanics, was thought to generate a null allele; we identified one patient with a homozygous IVS2-2A>G mutation who showed a mild deficiency of enzyme value in erythrocytes. One patient homozygous for Duarte 2 (p.N314D, IVS5+ 62G>A) is probably due to a partial uniparental disomy of chromosome 9. In addition, a novel mutation c.336T>C (p.S112R) was detected in one patient with severe enzymatic deficiency. Despite the small number of patients studied, our results suggest that classical galactosaemia shows low allelic heterogeneity in Mexican patients, in contrast what is observed in other Mendelian disorders such as cystinosis or autosomal dominant hypercholesterolaemia. This low allelic heterogeneity might be explained by a "population of origin" effect in the central region of Mexico, as has been described for phenylketonuria. © SSIEM and Springer 2008.