Classical homocystinuria is due to cystathionine beta-synthase (CBS) deficiency. More than 130 mutations, which differ in prevalence and severity, have been described at the CBS gene. Mutation p.I278T is very prevalent, has been found in all European countries where it has been looked for with the exception of the Iberian peninsula, and is known to respond to vitamin B-6. On the other hand, mutation p.T191M is prevalent in Spain and Portugal and does not respond to B-6. We analysed 30 pedigrees from Spain, Portugal, Colombia and Argentina, segregating for homocystinuria. the p.T191M mutation was detected in patients from all four countries and was particularly prevalent in Colombia. the number of p.T191M alleles described in this Study, together with those previously published, is 71. the prevalence of p.T191M among CBS mutant alleles in the different countries was: 0.75 in Colombia, 0.52 in Spain, 0.33 in Portugal, 0.25 in Venezuela, 0.20 in Argentina and 0.14 in Brazil. Haplotype analyses suggested a double origin for this mutation. No genotype-phenotype correlation other than the B-6-nonresponsiveness Could be established for the p.T191M mutation. Additionally,. three new mutations, p.M173V, p.I429del and c.69_70+8de110, were found. the p.M173V was associated with a mild, B-6-responsive, phenotype.Univ Barcelona, Fac Biol, Dept Genet, E-08028 Barcelona, SpainUniv Nacl Cordoba, Ctr Estud Metab Congenitas, Hosp Ninos, Cordoba, ArgentinaPontificia Univ Javeriana, Inst Genet Humana, Bogota, ColombiaUniv Antioquia, Fac Med, Depto Fisiol & Bioquim, Medellin, ColombiaFundac Estud Enfermedades Neurometab, Buenos Aires, DF, ArgentinaInst Genet Med Jacinto Magalhaes, Oporto, PortugalUniversidade Federal de São Paulo, UNIFESP, EPM, Dept Pediat, São Paulo, BrazilHosp Ramon y Cajal, Serv Pediat, Unidad Enfermedades Metab, Madrid, SpainHosp Univ Materno Infantil, Unidad Gastroenterol & Nutr, Las Palmas Gran Canaria, SpainHosp Infantil Le Fe, Unidad Nutr & Metab, Valencia, SpainHosp Clin Univ Santiago, Dept Pediat, Santiago de Compostela, SpainCorp Sanitaria Clin, Inst Bioquim Clin, Barcelona, SpainHosp St Joan Deu, Serv Bioquim, Barcelona, SpainUniversidade Federal de São Paulo, UNIFESP, EPM, Dept Pediat, São Paulo, BrazilWeb of Scienc
