Large deletions of the PROS1 gene in a large fraction of mutationnegative patients with protein S deficiency
Författare
Summary, in English
Protein S deficiency is an autosomal dominant disorder that results from mutations in the PROS I gene. Conventional mutation detection techniques fail to detect a pathogenic PROSI mutation in approximately 50% of cases. The present study investigates whether large deletions of PROS I are found in families where mutations in the PROS I gene have not been found despite sequencing. For this purpose, a dense set of SNP and microsatellite markers were used in segregation analysis to identify deletions. Large deletions were identified by this technique in three out of eight investigated families (38%). The deletions en-compassed at least 35 kb, 437 kb and 449 kb respectively. The deletions were confirmed by quantitative PCR. Haplotype analysis showed that the three large deletions and the five other disease haplotypes were all different. All of the eight disease haplotypes co-segregated with protein S deficiency, but each of the five non-deletion haplotypes were present also in normal individuals. In conclusion: Large deletions of PROS I are relatively common in protein S deficiency patients and screening for large deletions in PROS I mutation-negative individuals are therefore warranted.
Avdelning/ar
- Biologiska institutionen
- Klinisk kemi, Malmö
- MEMEG
- Allmänmedicin och klinisk epidemiologi
- Evolutionary Genetics
Publiceringsår
2005
Språk
Engelska
Sidor
951-957
Publikation/Tidskrift/Serie
Thrombosis and Haemostasis
Volym
94
Issue
5
Dokumenttyp
Artikel i tidskrift
Förlag
Schattauer GmbH
Ämne
- Cardiac and Cardiovascular Systems
Nyckelord
- protein S deficiency
- deletion
- mutation
- PROS I
Status
Published
Forskningsgrupp
- Clinical Chemistry, Malmö
- Family Medicine and Clinical Epidemiology
- Evolutionary Genetics
ISBN/ISSN/Övrigt
- ISSN: 0340-6245