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Mutational analysis of the cystathionine β‐synthase gene: A splicing mutation, two missense mutations and an insertion in patients with homocystinuria
Author(s) -
Gordon Ross B.,
Cox Anthony J.,
Dawson Paul A.,
Emmerson Bryan T.,
Kraus Jan P.,
Dudman Nicholas P. B.
Publication year - 1998
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/(sici)1098-1004(1998)11:4<332::aid-humu15>3.0.co;2-s
Subject(s) - homocystinuria , missense mutation , cystathionine beta synthase , biology , genetics , exon , compound heterozygosity , microbiology and biotechnology , mutation , transition (genetics) , point mutation , rna splicing , intron , gene , mutant , allele , splice site mutation , alternative splicing , amino acid , methionine , rna
RT‐PCR and direct sequence analyses were used to define mutations in the cystathionine β‐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. Hum Mutat 11:332, 1998. © 1998 Wiley‐Liss, Inc.