Detection of a novel deletion in the cystathionine β‐synthase (CBS) gene using an improved genomic DNA based method

FEBS Letters

Gaustadnes, Mette²  Rüdiger, Niels²  Jensen, Ole Kudsk¹  Rasmussen, Karsten²  Kraus, Jan P⁴  Ingerslev, Jørgen¹  Blom, Henk J³  Kluijtmans, Leo A.J³  Heil, Sandra G³ 

[1]Centre for Haemophilia and Thrombosis, Skejby University Hospital, Aarhus, Denmark

[2]Department of Clinical Biochemistry, Skejby University Hospital, Aarhus, Denmark

[3]Department of Pediatrics, University Hospital Nijmegen, Nijmegen, The Netherlands

[4]Department of Pediatrics, University of Colorado, Denver, CO, USA

关键词: Homocystinuria;    Cystathionine β-synthase;    Cystathionine β-synthase deficiency;    Mutation analysis;    Intronic sequence;    CBS;    cystathionine β-synthase;    DVT;    deep venous thrombosis;    tHcy;    total homocysteine in plasma;    PLP;    pyridoxal 5′-phosphate;    AdoMet;    S-adenosylmethionine;   

DOI  :  10.1016/S0014-5793(98)00743-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We elucidated the intron-exon boundaries of the 15 coding exons of the human cystathionine β-synthase (CBS) gene in order to establish an improved method based on PCR and direct sequencing for detection of CBS mutations. Using this method we identified the pathogenic mutations in two Danish siblings with CBS deficiency. Patients were compound heterozygotes: we detected the 833T→C mutation and a novel 22 bp deletion of exon 4 (493–514del) that introduces a frameshift and a stop codon immediately after the deletion. The deletion resulted in no detectable mRNA from this allele, as assessed by sequencing of cDNA. The established method represents an improvement of the existing method based on sequencing of cDNA because it permits the detection of mutations within the entire coding region of the CBS gene from a peripheral blood sample, including splice mutations and mutations resulting in the lack or a reduced amount of transcript.

【 授权许可】

Unknown