The cystathionine beta-synthase (CBS) mutation c.1224-2A>C in Central Europe: Vitamin B6 nonresponsiveness and a common ancestral haplotype.

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Linnebank M, Janosik M, Kozich V, Pronicka E, Kubalska J, Sokolova J, Linnebank A, Schmidt E, Leyendecker C, Klockgether T, Kraus JP, Koch HG

The cystathionine beta-synthase (CBS) mutation c.1224-2A>C in Central Europe: Vitamin B6 nonresponsiveness and a common ancestral haplotype.

Hum Mutat. 2004 Oct;24(4):352-3.

PubMed ID

15365998 [ View in PubMed

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Abstract

In homocystinuria due to cystathionine beta-synthase (CBS) deficiency, vitamin B6 response has been linked to distinct mutations and ruled out for others. The splice site mutation c.1224-2A>C leading to the deletion of exon 12 is predominantly found in patients from Central Europe, where it has been found on in average 14% of mutant alleles. In this study we analyzed the clinical picture in 17 CBS deficient carriers of c.1224-2A>C. Homozygotes for c.1224-2A>C did not respond to vitamin B6, while in compound heterozygotes the response to vitamin B6 depended on the mutation on the second allele. Maximum likelihood analysis revealed one common haplotype of the c.1224-2A>C alleles. Additionally, we report the four novel CBS mutations c.451G>A (p.Gly151?), c.740_769del (p.Lys247_Gly256del), c.862G>C (p.Ala288Pro) and c.1135C>T (p.Arg379Trp). In summary, the data of this study suggest that the CBS c.1224-2A>C allele confers vitamin B6 nonresponsiveness and that this mutant allele came from a common ancestor.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pyridoxal phosphate	Cystathionine beta-synthase	Protein	Humans	Unknown	Cofactor	Details

Polypeptides

Name	UniProt ID
Cystathionine beta-synthase	P35520	Details