Background: Cystathionine beta-synthase (CBS) deficiency is the most common cause of homocystinuria. However, no data are available concerning the molecular basis of this disease in Brazilian populations.
Methods: We studied 14 Brazilian patients from 11 unrelated families using a combined screening approach, involving restriction analysis, single-strand conformational polymorphism (SSCP) scanning, and sequencing.
Results: All patients presented homocysteine levels higher than 200 mumol/l before the beginning of treatment. The most common CBS gene mutations, p.G307S (c.919G > A) and p.I278T (c.833T > C), were evaluated and the allele c.919A was not found. One allele with the c.844 ins68 (4.5%) in the CBS gene was found. Three families (6 patients) presented the allele c.833 C (13.6%), without the insertion in the heterozygous state. SSCP scanning and sequencing showed 3 alleles p.T191M (13.64%) in 2 families. One allele with a novel mutation was found in exon 4 (c.168T > A) of the CBS gene (4.5%). We also analyzed c.677C > T and c.1298A > C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and the 2756A > G polymorphism in the methionine synthase (MTR) gene. The frequencies of mutated alleles were: 50% c.677T and 18.2% c.1298C for MTHFR, and 27.3% c.2756G for MTR.
Conclusion: In spite of the high level of racial mixing in the country, Brazilian homocystinuric patients did not present a high prevalence of the most common mutations described in the literature.