How we assess founder effect in patients with factor xiii deficiency in southeast iran
,1,* Akbar dorgalaleh
,2 Marzieh shakouri
,3 Majid fathi
,4 Mahla mir
,5 Omolbanin sargazi-aval
1. Cellular and Molecular Research Center, School of Allied Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
2. Department of Hematology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
3. Department of Hematology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
4. Department of Medical Biotechnology, School of Allied Medicine, Iran University of Medical Sciences. Tehran- Iran
5. Department of Hematology, School of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran
6. Faculty of Allied Medical Sciences, Zabol University of Medical Sciences, Zabol, Iran
Introduction (background): congenital factor xiii (fxiii) deficiency is an extremely rare bleeding disorder (rbd) with estimated prevalence of 1 per 2 million in the general population. this rbd causes different clinical manifestations such as intracranial hemorrhage (ich), recurrent miscarriage and umbilical cord bleeding (ucb). iran with more than 500 patients with fxiii deficiency has the highest global incidence of disease. sistan and baluchestan province in southeast of iran with 410 patients and with a rate of 1 per 7000 persons has the highest number of patients with fxiii deficiency not only in iran, but also in all over the world. our goal in the present study is diagnostic methods, especially to understand how founder effect influences on high rate of fxiii deficiency in southeast iran.
Materials and methods: in this study, suitable library sources like “congenital factor xiii deficiency”, “founder effect”, “molecular diagnosis of factor xiii deficiency”, “clinical presentation of factor xiii deficiency” and “rare bleeding disorders” were searched in databases like pubmed, google scholar, science direct and medline and finally 73 articles were selected for study out of 312.
Results: high incidence of this disease is possibly due to founder effect because consanguineous marriage is common in this area and p.trp187arg (c.559t> c) was observed as the only causative mutation of fxiii deficiency in this province. in suspected individuals to fxiii deficiency, haplotype analysis is an important step. for haplotype analysis, suitable and reliable genetic markers such as microsatellites (hum fxiii01 and humfxiiia02) and single nucleotide polymorphisms (snp) are suggested. for assessment of founder effect if: 1) candidate microsatellites and snp were meaningfully different in patient and control groups and 2. a unique haplotype was observed in the majority of patients, these can indicate genetic linkage between microsatellites and polymorphisms with causative mutation in southeast iran (trp187arg (c.559t> c). finally by analysis and comparison of attained haplotypes in patients and healthy individuals and checking of their similarities and differences, we can evaluate founder effect in patients with fxiii deficiency in southeast iran.
Discussion and conclusion: in the current study we tried to present a diagnostic method in order to evaluate present of founder effect in patients with fxiii deficiency in southeast iran via haplotype analysis using suitable genetic markers to make an effort in diagnosis, screening and genetic consultation of fxiii deficiency.
Factor xiii deficiency,, founder effect, haplotype analysis, consanguineous marriage