The p.T191M mutation of the CBS gene is highly prevalent among homocystinuric patients from Spain, Portugal and South America |
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| Authors: | Roser Urreizti Carla Asteggiano Marta Bermudez Alfonso Córdoba Mariana Szlago Carola Grosso Raquel Dodelson de Kremer Laura Vilarinho Vania D’Almeida Mercedes Martínez-Pardo Luís Peña-Quintana Jaime Dalmau Jaime Bernal Ignacio Briceño María Luz Couce Marga Rodés Maria Antonia Vilaseca Susana Balcells Daniel Grinberg |
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| Affiliation: | (1) Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Av. Diagonal, 645, 08028 Barcelona, Spain;(2) Centro de Estudio de las Metabolopatías Congénitas, Universidad Nacional de Córdoba, Hospital de Niños, Córdoba, Argentina;(3) Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia;(4) Depto de Fisiología y Bioquímica, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia;(5) Fundación para el Estudio de las Enfermedades Neurometabólicas, Buenos Aires, Argentina;(6) Instituto de Genética Médica Jacinto Magalhaes, Porto, Portugal;(7) Department of Pediatrics, Universidade Fereral de Sao Paulo-UNIFESP/EPM, Sao Paulo, Brazil;(8) Unidad de Enfermedades Metabólicas, Servicio de Pediatría, Hospital Ramón y Cajal, Madrid, Spain;(9) Unidad de Gastroenterología y Nutrición, Hospital Universitario Materno Infantil, Las Palmas de GC, Spain;(10) Unidad de Nutrición y Metabolopatías, Hospital Infantil La Fe, Valencia, Spain;(11) Departamento de Pediatría, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain;(12) Institut de Bioquímica Clínica, Corporació Sanitària-Clínic, Barcelona, Spain;(13) Servei de Bioquímica, Hospital Sant Joan de Déu, Barcelona, Spain |
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| Abstract: | Classical homocystinuria is due to cystathionine  -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 B6. On the other hand, mutation p.T191M is prevalent in Spain and Portugal and does not respond to B6. 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 B6-nonresponsiveness could be established for the p.T191M mutation. Additionally, three new mutations, p.M173V, p.I429del and c.69_70+8del10, were found. The p.M173V was associated with a mild, B6-responsive, phenotype. |
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| Keywords: | Homocystinuria CBS T191M mutation Latin-America Spain Portugal |
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