High frequency (71%) of cystathionine β-synthase mutation G307S in Irish homocystinuria patients

Gallagher, Paula; Ward, Pat; Tan, Soon Yu; Naughten, E. R.; Kraus, Jan P.; Sellar, Grant C.; McConnell, David J.; Graham, Ian; Whitehead, Alexander S.

doi:10.1002/humu.1380060211

Cited by 76 publications

(49 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This common mutation has been reported to be generally associated with pyridoxine responsiveness and a relatively mild clinical phenotype when present in the homozygous state (Shih et al 1995). On the other hand, a c.919G>A transition (p.G307S) is related to a more severe clinical phenotype and has been detected mainly in alleles from homocystinuric patients of Celtic origin, representing nearly 70% of the homocystinuric alleles in Ireland (Gallagher et al 1995). We previously reported the third most prevalent mutation, a c.572C>T transition (p.T191M), which is very common in the Iberian Peninsula, representing 50% of all Spanish homocystinuric alleles (Urreizti et al 2003).…”

Section: Introductionmentioning

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: Introductionmentioning

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

“…48 An allelic variation in the CBS gene, encoding a p.G307S amino-acid change, has been identified in homocystinuria patients of Celtic ancestry. 49,50 Another protein variant, p.I278T (rs5742905, c.833T4C), has also been identified in Celtic homocystinuria patients. 50,51 Heterozygotes for p.I278T, however, are believed to retain some degree of pyridoxine responsiveness to homocystinuria.…”

Section: Homocystinuria and Hypomethionemiamentioning

confidence: 99%

Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review

2009

View full text Add to dashboard Cite

“…45 The two most frequent mutations are 833T!C (I278T), which accounts for about one-quarter of all homocystinuric alleles and is the most common cause of homocystinuria in the Netherlands, 46 and 919G!A (G307S), which is the leading cause of homocystinuria in Ireland. 47 Reduced MS activity due to inborn errors of methylcobalamin transport or synthesis have been described as causing severe hyperhomocysteinaemia, but such cases are very rare. 48,49 In MTHFR de¢ciency, the clinical severity is correlated with the degree of enzyme de¢ciency, the most common clinical manifestation of MTHFR de¢ciency being developmental delay.…”

Section: Genetics Of Homocysteine Homocystinuriamentioning

confidence: 99%

Genetics of hyperhomocysteinaemia in cardiovascular disease

2003

View full text Add to dashboard Cite

Homocysteine, a sulphur amino acid, is a branch-point intermediate of methionine metabolism. It can be degraded in the transsulphuration pathway to cystathionine, or remethylated to methionine via the remethylation pathway. In both pathways, major genetic defects that cause enzyme de ciencies are associated with very high plasma homocysteine concentrations and excretion of homocystine into the urine. Mildly elevated plasma homocysteine concentrations are thought to be an independent and graded risk factor for both arterial occlusive disease and venous thrombosis. Genetic defects in genes encoding enzymes involved in homocysteine metabolism, or depletion of important cofactors or (co)substrates for those enzymes, including folate, vitamin B 12 and vitamin B 6 , may result in elevated plasma homocysteine concentrations. Plasma homocysteine concentrations are also in uenced by dietary and lifestyle factors. In the last decade, several studies have been conducted to elucidate the genetic determinants of hyperhomocysteinaemia in patients with cardiovascular disease. We report on both environmental and genetic determinants of hyperhomocysteinaemia and give a detailed overview of all the genetic determinants that have been reported to date.

show abstract

High frequency (71%) of cystathionine β-synthase mutation G307S in Irish homocystinuria patients

Cited by 76 publications

References 15 publications

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

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

Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review

Genetics of hyperhomocysteinaemia in cardiovascular disease

Contact Info

Product

Resources

About