Homocystinuria is an autosomal recessive disease most commonly caused by mutations in cystathionine beta-synthase (CBS). In this study we present the mutation analysis of 36 Colombian individuals from 10 unrelated kindred, with 11 individuals clinically classified as homocystinuric. Mutation analysis of the CBS gene revealed p.T191M, a prevalent mutation in Spain and Portugal, in the homozygous state in seven of the unrelated patients. Genotype-phenotype assessment of the p.T191M homozygous patients showed a high level of variability, including different severity in one pair of affected siblings. None of the patients responded biochemically to treatment with pharmacological doses of pyridoxine and folic acid as revealed by essentially unchanged homocysteine levels. This study offered a unique opportunity to study 18 heterozygous (p.T191M/wt) relatives of the homocystinuric patients. One atypical finding was that many of them presented with above average total homocysteine levels, putting them at an increased risk for vascular disease. Cryptorchidism was present in three of the cases, one of which presented also with Klinefelter syndrome. In addition to the previously described p.T191M mutation, a new mutation, p.A288T, was identified in a single individual. In this paper we present the first characterization, at a molecular level, of patients with homocystinuria from Colombia.
2006 Wiley-Liss, Inc.