Molecular analysis of homocystinuria in Brazilian patients

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.

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.

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.

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.