Hemophilia B (F9) Sequencing and Deletion/Duplication

Background Information for Hemophilia B (F9) Sequencing and Deletion/Duplication:
Characteristics: Severe deficiency of factor IX clotting activity is associated with spontaneous joint or deep tissue bleeding. Moderate or mild deficiency is associated with prolonged bleeding after tooth extractions, surgery, or injuries and recurrent or delayed wound healing.
Incidence: 1 in 25,000 males worldwide.
Penetrance: 100 percent in males and 10 percent in females.
Inheritance: X-linked recessive.
Cause: Pathogenic F9 gene mutations.
Clinical Sensitivity: 99 percent.
Methodology: Bidirectional sequencing of the entire F9 coding region and intron-exon boundaries and proximal promoter; Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large F9 deletions/duplications.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations and deep intronic mutations will not be detected. The breakpoints of large deletions/duplications will not be determined. Large deletions/duplications in exon 1 may not be detected. Mutations in genes other than F9 will not be detected.