Indirect Molecular Diagnosis of Congenital Factor ΧІІІ Deficiency by Candidate Microsatellites and Single Nucleotide Polymorphisms

Congenital factor XIII (FXIII) deficiency is one of the rarest bleeding disorders with a prevalence of one per 2 million in the general population. The disorder is accompanied by a high rate of life-threatening bleeding. Due to normal results of routine coagulation tests, diagnosis of the disorder is challenging, but molecular methods can be used for precise diagnosis. Direct mutation detection is the standard method for confirmation of the disorder, but indirect molecular diagnosis can be used as a fast and cost-benefit choice. In the present study, we described indirect molecular methods for molecular diagnosis of congenital FXIII deficiency.

For this study, a comprehensive literature review was performed on  PubMed, Embase, Web of Science, and Scopus databases using the following keywords: “indirect molecular diagnosis” with “rare bleeding disorder”, “coagulation factor XIII/13 deficiency”, “prenatal diagnosis” “rare bleeding disorder”, “molecular diagnosis”, “factor XIII/13 deficiency”, “indirect molecular diagnosis” “carrier detection”, and “factor XIII/13”. These words were used separately and in combination with each other.

A total of 293 papers were founded, among them 67 papers were selected for the study. Indirect molecular diagnostic approach can be done using candidate microsatellites and single nucleotide polymorphisms (SNP). This method can be used for prenatal diagnosis and carrier detection, especially in the areas with low economic resources. Polymorphic genetic markers associated with F13 gene like HumFXIII01, HumFXIIIA02, HumFXIIIB, rs7740009, and rs3024405 SNPs can be used for indirect molecular diagnosis of congenital FXIII deficiency. Finally, by comparing patient’s polymorphic markers with healthy individuals, diagnosis can be made.

It seems that indirect molecular diagnosis is a relatively reliable and cost-effective method for diagnosis of congenital FXIII deficiency in the areas with low economic resources.