F8 gene mutation profile in Indian hemophilia A patients: Identification of 23 novel mutations and factor VIII inhibitor risk association

Mutation Research
Patricia PintoShrimati Shetty

Abstract

'FVIII inhibitors', especially in severe hemophilia A (HA) patients, is a serious adverse effect that complicates their clinical management. Many genetic and non-genetic risk factors have been proposed for FVIII inhibitor development, diverse in different population groups. This is the first study in Indian hemophiliacs that analyzes inhibitor risk in relation to the complete F8 mutation profile, in a case-control study that included 145 Indian severe HA patients, i.e. 69 inhibitor positive (with 18 inhibitor concordant/discordant family members), and 58 inhibitor negative patients, after informed consent. While 53.54% (68/127) index cases were positive for intron 22 or intron 1 inversions, 55 causative F8 mutations were detected in the 59 inversion negative patients, of which 23 were novel mutations (in 24 patients) and 32 were reported earlier (in 35 patients). A higher incidence of mutations, in the C1 and C2 domains in inhibitor positive patients, and in the A1 domain in inhibitor negative patients was observed, though not significantly different. The study suggests that large F8 rearrangements (significantly higher in the inhibitor positive patients) pose the highest risk, while missense mutations (significantly higher in ...Continue Reading

References

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Apr 30, 2005·Clinical Chemistry·Liliana Carmen RossettiCarlos Daniel De Brasi
Jan 15, 2008·Clinica Chimica Acta; International Journal of Clinical Chemistry·Ravi RanjanRenu Saxena
Jan 17, 2009·Clinical Reviews in Allergy & Immunology·Kanjaksha Ghosh, Shrimati Shetty
Dec 25, 2012·Annals of Hematology·Patricia PintoShrimati Shetty
Jan 12, 2013·Thrombosis and Haemostasis·Rainer SchwaabJohannes Oldenburg
May 16, 2014·Blood Cells, Molecules & Diseases·Patricia PintoShrimati Shetty
Feb 26, 2015·Blood·Jan Astermark

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Citations

Nov 5, 2016·Indian Journal of Hematology & Blood Transfusion : an Official Journal of Indian Society of Hematology and Blood Transfusion·Hara Prasad Pati, Prashant Sharma
Feb 6, 2018·Journal of Thrombosis and Haemostasis : JTH·S SpenaUNKNOWN SIPPET Study Group
Sep 7, 2021·Frontiers in Cell and Developmental Biology·Sanchuan LuoDesheng Liang

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