Large deletions of the PROS1 gene in a large fraction of mutationnegative patients with protein S deficiency

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Abstract

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.

Detaljer

Författare
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Kardiologi

Nyckelord

Originalspråkengelska
Sidor (från-till)951-957
TidskriftThrombosis and Haemostasis
Volym94
Utgivningsnummer5
StatusPublished - 2005
PublikationskategoriForskning
Peer review utfördJa