D. Borgel et al., MOLECULAR-BASIS FOR PROTEIN-S HEREDITARY-DEFICIENCY - GENETIC-DEFECTSOBSERVED IN 118 PATIENTS WITH TYPE-I AND TYPE IIA DEFICIENCIES, The Journal of laboratory and clinical medicine, 128(2), 1996, pp. 218-227
Citations number
64
Categorie Soggetti
Medical Laboratory Technology","Medicine, General & Internal
Circulating protein S (PS) is partly bound to C4b-binding protein, and
only free PS can act as a cofactor for protein C (PC), a natural anti
coagulant. Two types of PS deficiencies are commonly observed in patie
nts with unexplained thrombosis, and they are characterized by having
both a low total PS level and a low free PS level (type I) or by havin
g only a low free PS level (type IIa). To elucidate the genetic mechan
isms responsible for these two plasma phenotypes, we screened 118 symp
tomatic patients with type I or type IIa PS deficiency for a PS gene c
oding sequence variation. A total of 34 mutations, 17 of which were no
vel, were identified in 65 propositi (70% in type I and 44% in type II
a). In type I deficiency, 29 different mutations were distributed thro
ughout the coding sequence. In type IIa deficiency, five different mis
sense mutations were clustered in exons XII and XIII, with a Ser 460 t
o Pro mutation accounting for most cases (82%). This points to a role
of the domain encoded by exons XII and XIII in the distribution betwee
n bound and free PS. The Ser 460 to Pro mutation was associated with t
he factor V Arg 506 to Gln mutation or a PC gene mutation in about hal
f the patients, suggesting a cooperative effect on clinical expression
.