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Thromb Haemost 1996; 75(03): 437-444
DOI: 10.1055/s-0038-1650293
Original Article
Schattauer GmbH Stuttgart

Five Novel Mutations of the Protein S Active Gene (PROS 1) in 8 Norman Families

Jérôme Duchemin
The INSERM U 428, Rouen, France
,
Jeanne-Yvonne Borg
1   Hôpital Charles Nicolle, Rouen, France
,
Delphine Borgel
The INSERM U 428, Rouen, France
,
Marc Vasse
1   Hôpital Charles Nicolle, Rouen, France
,
Hervé Lévèque
1   Hôpital Charles Nicolle, Rouen, France
,
Martine Aiach
The INSERM U 428, Rouen, France
,
Sophie Gandrille
The INSERM U 428, Rouen, France
› Author Affiliations
Further Information

Publication History

Received 01 August 1995

Accepted after resubmission 20 November 1995

Publication Date:
04 September 2018 (online)

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Summary

To further elucidate the molecular basis for hereditary thrombophilia, we screened the protein S active gene in 11 families with type I deficiency, using a strategy based on denaturating gradient gel electrophoresis (DGGE) of all the coding sequences. Fragments with an abnormal DGGE pattern were sequenced, and 5 novel mutations were identified in 8 families. The mutations were a 7-nucleotide deletion in exon II, a 4-nucleotide deletion in exon III, a T insertion in exon VII, a C to T transition transforming Leu 259 into Pro and a T to C transition transforming Cys 625 into Arg in 4 families. These mutations were the only sequence variations found in the propositus’ gene exons and co-segregated with the plasma phenotype. A total of 28 members of these 8 families were heterozygous for one of the 5 mutations. Twenty-four (58,5%) of the 41 deficient subjects over 18 years of age had clinical thrombophilia, whereas the 13 subjects under 18 were asymptomatic. Of the 28 subjects, 6 (21,5%) were also found to bear the factor V Arg 506 Gin mutation.

 

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