Hemophilia A (F8) 2 Inversions with Reflex to Sequencing and Reflex to Deletion/Duplication

Background Information for Hemophilia A (F8) 2 Inversions with Reflex to Sequencing and Reflex to Deletion/Duplication:
Characteristics: Severe deficiency of factor VIII 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 4,000-5,000 live male births worldwide; rare in females.
Inheritance: X-linked recessive. Of simplex cases, 85 percent of mothers are carriers and 10-15 percent of boys have a de novo mutation.
Penetrance: 100 percent in males and 10 percent in females.
Cause: Deleterious F8 gene mutations.
Clinical Sensitivity: 98 percent.
Methodology for Inversions: F8 intron 22-A and intron 1 inversions detected by inverse PCR and electrophoresis.
Methodology for Sequencing: Bidirectional sequencing of the F8 coding region and intron-exon boundaries.
Methodology for Deletion/Duplication: Multiplex ligation-dependent probe amplification (MLPA) to detect large deletions/duplications in the F8 coding region.
Analytical Sensitivity & Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region and deep intronic mutations, other than the F8 intron 22-A and intron 1 inversions, will not be detected. Deletions/duplications in exon 23 will not be detected.