Summary
Fasting and post-methionine load plasma total homocysteine concentrations were investigated in the parents of two homocystinuric patients. Three genetic mutations in the cystathionineβ-synthase gene were found. In the patient of family 1, a frequent Caucasian mutation, T833C, was found on one allele, while the mutation on the other allele has not yet been defined. In the patient of family 2, a mutation C569T, recently described by Sperandeo and colleagues, was found on one allele, while a novel mutation, G346A, was characterized on the other allele. The frequent gene mutation T833C was detected in a heterozygous mother who, surprisingly, exhibited strictly normal fasting and post-methionine load homocysteinaemia. In contrast, in the other family, we found a novel mutation (G346A) in the mother located near Lys 119, the putative binding site of phosphopyridoxal phosphate. This mother exhibited increased fasting and post-methionine load homocysteinaemia. These observations could explain the conflicting results reported for vascular pathologies in parents of homocystinuric patients and direct the search for genetic mutations in these vascular pathologies.
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Sperandeo, M.P., Candito, M., Sebastio, G. et al. Homocysteine response to methionine challenge in four obligate heterozygotes for homocystinuria and relationship with cystathionineβ-synthase mutations. J Inherit Metab Dis 19, 351–356 (1996). https://doi.org/10.1007/BF01799266
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DOI: https://doi.org/10.1007/BF01799266