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

• Main Authors: Ilić Nina, Krstić Aleksandra, Kuzmanović Miloš, Mićić Dragan, Konstantinidis Nada, Guć-Šćekić Marija
• Format: Article
• Language: English
• Published: Serbian Genetics Society 2013-01-01
• Series: Genetika
• Subjects: hemophilia A; intron 1 inversion; intron 22 inversion; frequency; Serbia
• Online Access: http://www.doiserbia.nb.rs/img/doi/0534-0012/2013/0534-00121301207I.pdf

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