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Genotyping of five Pakistani patients with severe inherited factor X deficiency

identification of two novel mutations

Borhany, Muniraa; Buthiau, Delphineb; Rousseau, Florenceb; Guillot, Olivierb; Naveena, Fatimaa; Abid, Madihaa; Shamsi, Tahira; Giansily-Blaizot, Murielb

Blood Coagulation & Fibrinolysis: November 2018 - Volume 29 - Issue 7 - p 622–625
doi: 10.1097/MBC.0000000000000764
ORIGINAL ARTICLES
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Congenital factor X deficiency is a rare coagulation defect characterized by variable bleeding tendency. The aim of the study was to give a first insight of F10 gene mutations in Pakistani probands. Direct sequencing and/or next-generation sequencing was performed on the coding regions, boundaries and 5’ and 3’ untranslated regions of the F10 gene in five severe factor X-deficient patients from Pakistan. All patients were born from consanguineous marriages and displayed FX:C levels below 2%. Sequencing revealed five different substitutions, including three previously reported p.Ala15Asp, p.Gly406Ser, and p.Gly420Arg missense variants, and also two novel variants: p.Cys57Arg and p.Gln175*. Though one genotype could not be characterized, we were able to confirm the inherited nature of the defect using familial studies. As the copy number variations were ruled out, we hypothesized the presence of deep intronic mutants that might have escaped detection from sequencing or abnormalities in epigenetic regulation. Three patients presented with severe clinical symptoms, in the early days of life, whereas two presented only with trauma-provoked bleeds and bruises later in life. Those patients with milder forms bore the p.Gly406Ser at the homozygous state and F10 unknown alleles, respectively. F10 mutation spectrum in Pakistan is heterogeneous as seen in other populations. Identification of the F10 mutations is important for genetic counseling and prenatal diagnosis in subsequent pregnancies.

aDepartment of Haematology, Haemostasis and Thrombosis of the National Institute of Blood Disease and Bone Marrow Transplantation (NIBD), Karachi, Pakistan

bDépartement d’hématologie biologique, CHU Montpellier, Univ Montpellier, Montpellier, France

Correspondence to Muriel Giansily-Blaizot, Département d’hématologie biologique, CHU de Montpellier, Hôpital Saint Eloi, 80 avenue Augustin Fliche, 34295 Montpellier cedex 5, France. Tel: +33 467337031; fax: +33 467337036; e-mail: m-giansily@chu-montpellier.fr

Received 6 February, 2018

Revised 7 June, 2018

Accepted 5 July, 2018

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