Haemophilia A is an X-linked genetic disorder that affects males and is associated with abnormalities of coagulation factor VIII (Factor VIII) and the corresponding F8 gene, resulting in decreased clotting activity and delayed wound healing. The symptoms may be severe or milder and may occur early in life or later. Diagnosis in male patients is based on the finding of reduced factor VIII activity in the blood and identification of a pathogenic mutation in the F8 gene. Female carriers are usually asymptomatic and may be reliably identified only through genetic testing.
Haemophilia B is also an X-linked genetic disorder that affects males and is associated with abnormalities of coagulation factor IX (Factor IX) and the corresponding F9 gene, with clinical symptoms virtually identical to those of hemophilia A. More than 900 F9 gene mutations have been reported, while mutations occurring at the first part of the gene sequence cause an unusual form of hemophilia known as haemophilia B Leyden. Individuals with these mutations are born with very low levels of functional coagulation Factor IX, but hormonal changes during puberty cause a gradual increase in the levels of this protein. As a result, adults with hemophilia B Leyden rarely exhibit clotting abnormalities and are generally not affected.
We perform DNA sequence analysis, via Next Generation Sequencing (NGS) on a Genome Analyzer – Ion Proton platform, of all exons and intron-exon junctions/splice sites of the F8 and F9 genes, in combination with the detection of the intron 1 and intron 22 inversions of the F8 gene, allowing us to detect >98% of all pathogenic mutations of the genes through the use of specially developed bioinformatics tools,
Where possible and/or necessary, we carry out additional MLPA analysis in order to detect deletions/duplications of the genes (please consult the final test report).
The test is highly sensitive and complex, so it is necessary that the results are assessed by a specialized team of clinical and molecular geneticists, in order to ensure safe and reliable testing.
Proper clinical genetic assessment and genetic counseling, both before and after testing, is essential in order to determine the optimum testing strategy and also to communicate properly the concepts of pathological and normal.