High Prevalence of the I278T Mutation of the Human Cystathionine β-Synthase Detected by a Novel Screening Application

Michael Linnebank; Anja Homberger; Ralf Junker; Ulrike Nowak-Goettl; Erik Harms; Hans G. Koch

doi:10.1055/s-0037-1615951

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 85(06): 986-988
DOI: 10.1055/s-0037-1615951

Review Article

Schattauer GmbH

High Prevalence of the I278T Mutation of the Human Cystathionine β-Synthase Detected by a Novel Screening Application

Authors

Michael Linnebank

¹Klinik und Poliklinik für Kinderheilkunde, Westfälische Wilhelms-Universität Münster, Münster, Germany
Anja Homberger

¹Klinik und Poliklinik für Kinderheilkunde, Westfälische Wilhelms-Universität Münster, Münster, Germany
Ralf Junker

²Institut für Klinische Chemie und Laboratoriumsmedizin, Westfälische Wilhelms-Universität Münster, Münster, Germany
Ulrike Nowak-Goettl

¹Klinik und Poliklinik für Kinderheilkunde, Westfälische Wilhelms-Universität Münster, Münster, Germany
Erik Harms

¹Klinik und Poliklinik für Kinderheilkunde, Westfälische Wilhelms-Universität Münster, Münster, Germany
Hans G. Koch

¹Klinik und Poliklinik für Kinderheilkunde, Westfälische Wilhelms-Universität Münster, Münster, Germany

Abstract

Summary

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 I278T corresponding to a calculated frequency of homozygosity of 1:17.800. Our data indicate that homocystinuria due to cystathionine β-synthase deficiency is a frequently unrecognized disorder resulting in a high risk of thromboembolic events.

Key words

Homocystinuria - homocysteine - cystathionine β-synthase - mutation screening

Full Text

References

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