Identification of two different mutations causing protein S deficiency in two unrelated Belgian families using a nonisotopic scanning and sequencing method.
Hereditary protein S deficiency is a risk factor for developing recurrent venous thromboembolic disease and is caused by a defect in the protein S 1 (PROS1) gene. Identification of the mutation in the PROS1 gene can overcome diagnostic uncertainty in family members with borderline protein S levels. We describe a novel nonisotopic method for molecular diagnosis of protein S deficiency, using fluorescein-labeled amplification and sequencing primers. As a first step, all exons of the PROS1 gene are selectively amplified, and heteroduplex analysis is performed. As a second step, all exons are analyzed by direct sequencing. Using this method, we have characterized the molecular defect in two Belgian families with hereditary protein S deficiency type I: a frameshift mutation in exon XIV (1881insTC) and a missense mutation caused by a T-to-C transition, resulting in substitution of Leu405 by Pro (L405P).
Department of Medical Genetics, University Hospital Gent, Belgium. Ludwine.Messiaen@rug.ac.be
L
L
Messiaen
T
T
Callens
G
G
Baele
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D017293:Protein S / Q000235:genetics*; D018455:Protein S Deficiency / Q000235:genetics*; D017421:Sequence Analysis / Q000379:methods*
D017293:Protein S