Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.1.22 (cystathionine beta-synthase)
 965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cystathionine beta-synthase (CBS) deficiency is an autosomal recessive disorder associated with multisystem clinical disease. We analyzed PCR amplified products from patients' RNA and genomic DNA. Direct sequencing of the entire coding region of the CBS gene revealed a G-919 to A transition in exon 8, resulting in replacement of Gly 307 by Ser (G307S) in the protein. The mutation was detected in one allele of patient L171 of French/Scottish ancestry and in both alleles of patient L198 of Irish ancestry. Amplifying and sequencing exon 8 from the genomic DNA showed that both parents of L198 were heterozygotes for G307S. The pathogenicity of the mutation was demonstrated in an expression experiment. The mutant protein was apparently stable in E.coli extracts and lacked catalytic activity. Sequencing of exon 8 revealed the G307S mutation in five additional families. All patients have pyridoxine nonresponsive homocystinuria. We have now observed this mutation in 9 of 52 apparently unrelated alleles of varied ethnic backgrounds. All 9 are from patients with Celtic (Irish/English/Scottish/French) ancestry in either one or both parents. The G307S mutation was detected in 50% (9 of 18) of the Celtic alleles in our series. The second mutation found in exon 8 is the I278T mutation, which was described previously in one allele of a pyridoxine responsive patient. This missense mutation was detected in one allele of a pyridoxine nonresponsive patient and in both alleles of a pyridoxine responsive patient. The latter suggests that I278T is probably associated with pyridoxine responsiveness.
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PMID:Molecular basis of cystathionine beta-synthase deficiency in pyridoxine responsive and nonresponsive homocystinuria. 750 2

Hyperhomocysteinemia occurs in approximately 30% of the patients with premature occlusive arterial disease (POAD). Some of these exhibit significantly reduced fibroblast cystathionine beta-synthase (CBS) activities, suggesting that they may be heterozygous for CBS deficiency. To test this possibility, we studied cDNA derived from four well characterized patients with POAD, exhibiting hyperhomocysteinemia and reduced CBS activities, from four normal controls, and from four obligatory heterozygotes for CBS deficiency. Lysates of individual colonies of E.coli, containing full-length PCR-amplification products in the expression vector, pKK388.1, were tested for CBS activity. cDNA from at least seven of the eight possible independent POAD alleles encoded catalytically active, stable CBS which exhibited normal response to both PLP and AdoMet. The sequences of all 3'-untranslated regions of all seven isolated POAD alleles were identical to the normal, 'wild-type' CBS sequences. The results of the expression studies were confirmed for one POAD patient by determining the full-length cDNA sequences for both alleles; these were entirely normal over the complete length of the cDNA. In contrast, the screening method correctly distinguished mutant from normal alleles in all four obligatory heterozygotes studied. We conclude that CBS mRNAs from POAD individuals are free from inactivating mutations, including all 33 previously identified in heterozygous carriers and homocystinuric patients.
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PMID:Hyperhomocysteinemia in premature arterial disease: examination of cystathionine beta-synthase alleles at the molecular level. 763 11

Homocystinuria due to cystathionine beta-synthase (CBS) deficiency is an inherited disorder of homocysteine transsulfuration, which manifests by neurological, vascular and connective tissue involvement. So far, 130 pathogenic mutations have been recognized in the CBS gene. We examined 10 independent alleles in Polish patients suffering from CBS deficiency, and we detected four already described mutations (c.1224-2A>C, c.684C>A, c.833T>C, and c.442G>A) and two novel mutations (c.429C>G and c.1039+1G>T). The pathogenicity of the novel mutations was demonstrated by expression in E.coli. This is the first published communication on mutations leading to CBS deficiency in Poland.
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PMID:Identification and functional analysis of two novel mutations in the CBS gene in Polish patients with homocystinuria. 1514 73