Molecular defect in a patient with pyridoxine-responsive homocystinuria

Kozich,; R, de Franchis; Jp, Kraus

doi:10.1093/hmg/2.6.815

Cited by 23 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The p.I429del mutation was present, in compound heterozygosis with p.A114V, in an Argentinean patient (#38) presenting a mild phenotype and a positive response to B 6 . The fact that the accompanying mutation is known to be associated with a mild phenotype (Kozich et al 1993;) precludes our drawing conclusions on the effects of p.I429del. Regarding the third novel mutation identified, c.69_70+8del10, the fact that the 10-bp deletion included the donor site of intron 1 supports a pathogenic role for this change.…”

Section: Discussionmentioning

confidence: 99%

The p.T191M mutation of the CBS gene is highly prevalent among homocystinuric patients from Spain, Portugal and South America

et al. 2006

View full text Add to dashboard Cite

Classical homocystinuria is due to cystathionine b-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+8del10, were found. The

show abstract

Section: Discussionmentioning

confidence: 99%

The p.T191M mutation of the CBS gene is highly prevalent among homocystinuric patients from Spain, Portugal and South America

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Nature of the mutations: We have identified 14 mutations in homocystinuric patients to date (KoEich and Kraus 1992;de Franchis et al 1993;Hu et al 1993;Koch et al 1993;Ko~ich et al 1993;Marble et al 1993;Sebastio et al 1993;Gallagher et al 1994). Table 1 lists these mutations by type, by number of independent alleles discovered, by exon, and by ethnic origin of the patients.…”

Section: Cbs Mutationsmentioning

confidence: 99%

Molecular basis of phenotype expression in homocystinuria

Kraus

1994

J of Inher Metab Disea

103

View full text Add to dashboard Cite

Cystathionine beta-synthase (CBS) deficiency is the most common cause of homocystinuria in humans. The human gene maps to chromosome 21q22.3 and encodes the CBS subunit of 551 amino acid residues (63kDa). CBS, a tetramer of these subunits, binds its two substrates, homocysteine and serine, and three additional ligands: pyridoxal 5'-phosphate, S-adenosylmethionine, and haem. Screening for mutations by expressing patient cDNA segments in E. coli permitted us to separate the parental CBS alleles, localize each mutation within one third of the cDNA, and functionally analyse the mutant protein. Using this method we identified the first 14 mutations in homocystinuria. The most common mutation in patients of predominantly 'Celtic' origin is the G919A transition which substitutes serine for glycine 307.

show abstract

“…Cystathionine beta-synthase gene CBS sequencing revealed a compound heterozygosis for a previously described mutation (p.Ile278Thr)[3] and a novel mutation (p.Met89Lys). Vitamin B6 and folic acid were administered (450 mg pro day and 15 mg pro day, respectively) with complete psychotic symptoms remission in about 2 months.…”

mentioning

confidence: 87%