1994
DOI: 10.1007/bf00711354
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Molecular basis of phenotype expression in homocystinuria

Abstract: 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 mu… Show more

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Cited by 103 publications
(52 citation statements)
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References 14 publications
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“…No well-defined correlation between genotype and phenotype has been established in CBS deficiency. 9,27 However, it appears that homozygosity for the 919G3 A (G307S) mutation correlates with pyridoxine nonresponsiveness, 28 whereas homozygosity for the 833T3 C mutation correlates with pyridoxine responsiveness, in agreement with treatment results in our study family. 10,19 Yet exceptions from this rule exist.…”
Section: Pyridoxine Responsivenesssupporting
confidence: 89%
“…No well-defined correlation between genotype and phenotype has been established in CBS deficiency. 9,27 However, it appears that homozygosity for the 919G3 A (G307S) mutation correlates with pyridoxine nonresponsiveness, 28 whereas homozygosity for the 833T3 C mutation correlates with pyridoxine responsiveness, in agreement with treatment results in our study family. 10,19 Yet exceptions from this rule exist.…”
Section: Pyridoxine Responsivenesssupporting
confidence: 89%
“…A total of nine variations were detected, and four of them, T257M, R336C, G347S, and T353M, had been previously reported Gaustadnes et al 2002;Dawson et al 1997;Kraus 1994). Five variations, R18C, L154Q, A155V, A288T, and del234D, were novel (Table 2).…”
Section: Mutation Analysismentioning
confidence: 65%
“…In addition, all the patients and their families showed c.1080C/T polymorphism, and c.699C/T polymorphism was found in patient 4 and her family. The c.1080C/T and c.699C/T are known as benign polymorphisms in CpG islands (Kraus 1994).…”
Section: Discussionmentioning
confidence: 99%
“…Human CBS also forms multimers, coordinates heme with a bound iron, and contains a regulatory domain that binds the metabolite AdoMet as a possible regulatory mechanism (Shan and Kruger 1998;Meier et al 2001;Christopher et al 2002;Scott et al 2004;Chen et al 2006;Sen and Banerjee 2007). These features suggest control points for enzyme regulation and function, or targets for nutritional and pharmaceutical therapies, that CBS alleles may affect differently.Directed sequencing efforts of patients afflicted with homocystinuria have produced a large catalog of alleles (Kraus et al 2012), with both common and rare alleles (Mudd et al 1985;Kraus 1994;Gallagher et al 1995Gallagher et al , 1998. However, clinical association does not guarantee causality.…”
mentioning
confidence: 99%
“…Directed sequencing efforts of patients afflicted with homocystinuria have produced a large catalog of alleles (Kraus et al 2012), with both common and rare alleles (Mudd et al 1985;Kraus 1994;Gallagher et al 1995Gallagher et al , 1998. However, clinical association does not guarantee causality.…”
mentioning
confidence: 99%