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Frequency of the p. G ly262 A sp mutation in congenital F actor X deficiency
Author(s) -
Epcacan Serdar,
Menegatti Marzia,
Akbayram Sinan,
Cairo Andrea,
Peyvandi Flora,
Oner Ahmet F.
Publication year - 2015
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.12511
Subject(s) - missense mutation , partial thromboplastin time , medicine , gastroenterology , factor x , mutation , prothrombin time , autosomal recessive trait , mutation testing , incidence (geometry) , pediatrics , coagulation , genetics , gene , biology , platelet , thrombin , physics , optics
Congenital factor X ( FX ) deficiency is a rare bleeding disorder inherited as an autosomal recessive trait with an incidence of 1 : 500 000–1 000 000. A total or partial deficiency of FX causes an impairment of clot formation, leading to a haemorrhagic disease, which manifests with bleeding symptoms of different severity, also unprovoked. Aim We analysed the clinical manifestations, laboratory phenotype and genotype in 12 patients from T urkey affected with severe FX deficiency. Methods Prothrombin time ( PT ), activated partial thromboplastin time ( APTT ), FX activity ( FX :C) and FX antigen level ( FX :Ag) were measured, and mutation analysis was performed for all patients. Results The most frequent bleeding episodes in patients were epistaxis and easy bruising (11/12, 91%), followed by haemarthroses (10/12, 83%). FX :C was <1% in 11 patients, and 4% in one. FX :Ag was reduced in all patients, consistent with type II deficiency. Direct sequencing of the factor X gene ( F10 ) identified two different mutations: the novel 33 bp in‐frame deletion p.Thr176_Gln186, c.526_558del, which seems to be associated with milder bleeding symptoms and the c.785G>A, p.Gly262Asp missense mutation (previously reported as Gly222Asp), which is associated with severe bleeding symptoms. Conclusion The p.Gly262Asp missense mutation was identified in 11 of the 12 patients in this study. Previously published cases on the same p.Gly262Asp mutation were I ranian patients originating from the border between T urkey and I ran suggesting that this mutation may be candidate as a good tool for mutational screening analysis in this area.