Page 361 - Essential Haematology

Chapter 26 Coagulation disorders / 347

X

3' tel 3' mRNA3'
F8B FVIII
FVIII
cen F8A F8B
5'
F8A
F8A

5' mRNA5'
q28 F8A FVIII
F8A F8A
tel tel tel

Figure 26.2 The mechanism of the fl ip - tip inversion leading to disruption of the factor VIII gene. (Left) The

orientation of the factor VIII gene is shown with the three copies of gene A (F8A) in this region (one within an
intron 22 and two near the telomere). (Middle) During spermatogenesis at meiosis, the single X pairs with the Y
chromosome in the homologous regions. The X chromosome is longer than the Y and there is nothing to pair
with most of the long arm of X. The chromosome undergoes homologous recombination between the A genes.
(Right) The fi nal result is that the factor VIII gene is disrupted. cen, centromeric end; tel, telomere; the arrows
indicate the direction of transcription from the A gene.

Figure 26.4 Haemophilia A showing severe disability.
Figure 26.3 Haemophilia A: acute haemarthrosis of

The left knee is swollen with posterior subluxation of
the right knee joint with swelling of the suprapatellar
the tibia on the femur. The ankles and feet show
region. There is wasting of the quadriceps muscles,
residual deformities of talipes equinus, with some
particularly on the left.
cavus and associated toe clawing. There is general-
ized muscle wasting. The scar on the medial side of
the left lower thigh is the site of a previously excised
pseudotumour.