High prevalence of the I278T mutation of the human cystathionine beta-synthase detected by a novel screening application.
Classical homocystinuria due to cystathionine beta-synthase deficiency is one of the disorders revealing a high risk of thromboembolic events and vascular disease. This autosomal-recessively inherited metabolic disorder is considered to be rare with an estimated prevalence of 1:130,000 in the German population. In this study, we developed a novel multiplex PCR generating allele specific fragment lengths to analyse individual genotypes of the two most frequent cystathionine beta-synthase alterations, the I278T mutation, which is worldwide found on up to the half of homocystinuric alleles, and the adjacent polymorphism 844ins68. Screening of 200 unrelated German control subjects revealed a frequency of heterozygosity of 1.5% for 1278T corresponding to a calculated frequency of homozygosity of 1:17.800. Our data indicate that homocystinuria due to cystathionine beta-synthase deficiency is a frequently unrecognized disorder resulting in a high risk of thromboembolic events.
Linnebank
M
M
Klinik und Poliklinik für Kinderheilkunde, Westfällische Wilhelms-Universität Münster, Germany.
Homberger
A
A
Junker
R
R
Nowak-Goettl
U
U
Harms
E
E
Koch
H G
HG
D003541:Cystathionine beta-Synthase / Q000235:genetics*; D005787:Gene Frequency; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006579:Heterozygote; D006712:Homocystinuria / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D015995:Prevalence
D003541:Cystathionine beta-Synthase