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Detection of a novel deletion in the cystathionine β‐synthase (CBS) gene using an improved genomic DNA based method 1
Author(s) -
Gaustadnes Mette,
Kluijtmans Leo A.J,
Jensen Ole Kudsk,
Rasmussen Karsten,
Heil Sandra G,
Kraus Jan P,
Blom Henk J,
Ingerslev Jørgen,
Rüdiger Niels
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00743-1
Subject(s) - frameshift mutation , exon , genetics , biology , cystathionine beta synthase , gene , coding region , microbiology and biotechnology , genomic dna , complementary dna , mutation , intron , dna sequencing , splice , amino acid , methionine
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.