The p.T191M mutation of the CBS gene is highly prevalent among homocystinuric patients from Spain, Portugal and South America.
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 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.
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Av. Diagonal, 645, 08028, Barcelona, Spain.
Roser
R
Urreizti
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Av. Diagonal, 645, 08028, Barcelona, Spain.|Centro de Estudio de las Metabolopatías Congénitas, Universidad Nacional de Córdoba, Hospital de Niños, Córdoba, Argentina.
Carla
C
Asteggiano
Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia.
Marta
M
Bermudez
Depto de Fisiología y Bioquímica, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
Alfonso
A
Córdoba
Fundación para el Estudio de las Enfermedades Neurometabólicas, Buenos Aires, Argentina.
Mariana
M
Szlago
Centro de Estudio de las Metabolopatías Congénitas, Universidad Nacional de Córdoba, Hospital de Niños, Córdoba, Argentina.
Carola
C
Grosso
Centro de Estudio de las Metabolopatías Congénitas, Universidad Nacional de Córdoba, Hospital de Niños, Córdoba, Argentina.
Raquel Dodelson
RD
de Kremer
Instituto de Genética Médica Jacinto Magalhaes, Porto, Portugal.
Laura
L
Vilarinho
Department of Pediatrics, Universidade Fereral de Sao Paulo-UNIFESP/EPM, Sao Paulo, Brazil.
Vania
V
D'Almeida
Unidad de Enfermedades Metabólicas, Servicio de Pediatría, Hospital Ramón y Cajal, Madrid, Spain.
Mercedes
M
Martínez-Pardo
Unidad de Gastroenterología y Nutrición, Hospital Universitario Materno Infantil, Las Palmas de GC, Spain.
Luís
L
Peña-Quintana
Unidad de Nutrición y Metabolopatías, Hospital Infantil La Fe, Valencia, Spain.
Jaime
J
Dalmau
Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia.
Jaime
J
Bernal
Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia.
Ignacio
I
Briceño
Departamento de Pediatría, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain.
María Luz
ML
Couce
Institut de Bioquímica Clínica, Corporació Sanitària-Clínic, Barcelona, Spain.
Marga
M
Rodés
Servei de Bioquímica, Hospital Sant Joan de Déu, Barcelona, Spain.
Maria Antonia
MA
Vilaseca
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Av. Diagonal, 645, 08028, Barcelona, Spain.
Susana
S
Balcells
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Av. Diagonal, 645, 08028, Barcelona, Spain. dgrinberg@ub.edu.
Daniel
D
Grinberg
D000483:Alleles; D016009:Chi-Square Distribution; D003105:Colombia / Q000453:epidemiology; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D005787:Gene Frequency; D006239:Haplotypes; D006712:Homocystinuria / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D009154:Mutation; D010375:Pedigree; D011174:Portugal / Q000453:epidemiology; D015995:Prevalence; D013030:Spain / Q000453:epidemiology
D003541:Cystathionine beta-Synthase