doiSerbia

Identification of intron 1 and intron 22 inversions of factor VIII gene in Serbian patients with hemophilia A

Ilić Nina (Institut za zdravstvenu zaštitu majke i deteta Srbije “Dr Vukan Čupić”, Beograd)
Krstić Aleksandra (Institut za zdravstvenu zaštitu majke i deteta Srbije “Dr Vukan Čupić”, Beograd)
Kuzmanović Miloš (Institut za zdravstvenu zaštitu majke i deteta Srbije “Dr Vukan Čupić”, Beograd)
Mićić Dragan (Institut za zdravstvenu zaštitu majke i deteta Srbije “Dr Vukan Čupić”, Beograd)
Konstantinidis Nada (Institut za zdravstvenu zaštitu dece i omladine Vojvodine, Novi Sad)
Guć-Šćekić Marija (Institut za zdravstvenu zaštitu majke i deteta Srbije “Dr Vukan Čupić”, Beograd)

Hemophilia A (HA) is a common X-linked recessive bleeding disease caused by mutations of FVIII gene. Inversion of intron 1 (inv1) and intron 22 (inv22) are recurrent mutations in severe HA, causing 50% of cases. Inv1 has been reported to occur in 2-5% and inv 22 in 45% of severe HA patients. Our objective was to determine, for the first time in Serbia, the frequency of inv1 and inv22 in a group of severe HA patients and to compare these data with those from other countries. Study subjects were 50 HA patients, diagnosed and treated from April 2009 to June 2012 at Mother and Child Health Care Institute of Serbia “Dr Vukan Cupic” (IHS) and Institute for Child and Youth Health Care of Vojvodina (IHV).The presence of inv1 and inv22 was analyzed using Inverse shifting PCR (IS-PCR). Our results revealed that the frequencies of inv1 and inv22 in the cohort of Serbian patients were 6 % and 42% (34% of inv22 type I and 8% of inv22 type II) respectively . These frequencies were in line with those found in other populations. Carrier status analyses of 65 family members (mothers and sisters) showed the de novo inversion of intron 22 in one patient. Genetic Counseling Units of IHS and IHV provide the adequate genetic advice to all HA affected patients and their family members.

Keywords: hemophilia A, intron 1 inversion, intron 22 inversion, frequency, Serbia

Projekat Ministarstva nauke Republike Srbije, br. 173046 i br. 175056