Indirect molecular diagnosis of congenital factor ΧІІІ deficiency by candidate microsatellites and single nucleotide polymorphisms

Hojat Shahraki,1,* Akbar dorgalaleh,2 Omolbanin sargazi-aval,3 Marzieh shakouri,4 Majid fathi,5 Maryam daneshi,6

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. Faculty of Allied Medical Sciences, Zabol University of Medical Sciences, Zabol, Iran
4. Department of Hematology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
5. Department of Medical Biotechnology, School of Allied Medicine, Iran University of Medical Sciences. Tehran- Iran
6. Msc of hematology, Department of laboratory sciences, School of Allied Medicine, Arak University of Medical Sciences, Arak, Iran

Abstract

Introduction

Introduction (background): congenital factor xiii (fxiii) deficiency is one of the rare bleeding disorders (rbd) with a prevalence of 1 per 2 million individuals with different clinical presentations such as intracranial hemorrhage, umbilical cord bleeding and recurrent spontaneous miscarriage. according to inheritance pattern (autosomal recessive) of the disease, the prevalence of the disorder is significantly high in areas with high rate of consanguineous marriage. purpose of current study is comprehensive and precise analysis of indirect molecular diagnosis of congenital factor ΧІІІ deficiency and provide a diagnostic method especially in developing countries.

Methods

Materials and methods: in this study, by searching suitable keywords like “coagulation factor xiii deficiency”, “rare bleeding disorder”, “molecular diagnosis of factor xiii deficiency”, “indirect molecularddiagnosis in databases like pubmed, google scholar, science direct , medline and ultimately, 69 articles were selected for study from 293.

Results

Results: in developed countries utilization of direct molecular diagnosis method (direct sequence analysis) make detection of mutation possible but in developing countries, in addition to direct mutation detection, more cost-effective methods such as indirect molecular diagnosis can be used. this indirect molecular diagnosis by candidate microsatellites and single nucleotide polymorphisms (snp) can be used for prenatal diagnosis (pnd) and carrier detection. establishment of informative and intragenic markers is required to elevate the probability of co-segregation with pathogenic mutations. we can use polymorphic genetic markers associated to fxiii gene in these methods like humfxiii01, humfxiiia02, humfxiiib and candidate short tandem repeat (str) and snp (like rs7740009, rs3024405). finally by comparing patients polymorphic markers versus healthy individuals, prenatal diagnosis and carrier detection can be made.

Conclusion

discussion and conclusion: it seems that indirect molecular diagnosis is a relatively reliable and cost-effective method for diagnosis of congenital fxiii deficiency in countries with low economical resources.

Keywords

Coagulation factor xiii deficiency, clinical presentations, rare bleeding disorder, diagnosis