title: Mutational analysis of the cystathionine beta-synthase gene: a splicing mutation, two missense mutations and an insertion in patients with homocystinuria. Mutations in brief no. 120. Online.
abstract: RT-PCR and direct sequence analyses were used to define mutations in the cystathionine beta-synthase (CBS) gene in two unrelated male patients with vitamin B6 nonresponsive homocystinuria. Both patients were compound heterozygotes for CBS alleles containing point mutations. One patient had a maternally derived G->A transition in the splice-donor site of intron 1, resulting in aberrant splicing of CBS mRNA. The other allele contained a missense mutation resulting in the previously reported E144K mutant CBS protein. The second patient had a maternally derived 4 bp insertion in exon 17, predicted to cause a CBS peptide of altered amino acid sequence. A 494G->A transition was found in exon 4 of the other allele, predicting a C165Y substitution. Expression of recombinant CBS protein, containing the C165Y mutation, had no detectable catalytic activity. Each mutation was confirmed in genomic DNA.
authors.affiliation: Department of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane 4102, Australia. agordon@ozemail.com.au
authors.forename: R B
authors.initials: RB
authors.lastname: Gordon
authors.forename: A J
authors.initials: AJ
authors.lastname: Cox
authors.forename: P A
authors.initials: PA
authors.lastname: Dawson
authors.forename: B T
authors.initials: BT
authors.lastname: Emmerson
authors.forename: J P
authors.initials: JP
authors.lastname: Kraus
authors.forename: N P
authors.initials: NP
authors.lastname: Dudman
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D003541:Cystathionine beta-Synthase / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D004251:DNA Transposable Elements / Q000235:genetics; D006712:Homocystinuria / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004251:DNA Transposable Elements; D003541:Cystathionine beta-Synthase