Premium
The cystathionine β‐synthase (CBS) mutation c.1224‐2A>C in Central Europe: Vitamin B 6 nonresponsiveness and a common ancestral haplotype
Author(s) -
Linnebank Michael,
Janosik Miroslav,
Kozich Viktor,
Pronicka Ewa,
Kubalska Jolanta,
Sokolova Jitka,
Linnebank Anja,
Schmidt Eva,
Leyendecker Christina,
Klockgether Thomas,
Kraus Jan Peter,
Koch Hans Georg
Publication year - 2004
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9280
Subject(s) - cystathionine beta synthase , biology , haplotype , genetics , allele , compound heterozygosity , mutation , exon , mutant , microbiology and biotechnology , gene , amino acid , methionine
In homocystinuria due to cystathionine β‐synthase (CBS) deficiency, vitamin B 6 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 B 6 , while in compound heterozygotes the response to vitamin B 6 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. © 2004 Wiley‐Liss, Inc.