Jeremy N Wells1, Kerryn M Weekes1, Wendy M Hutchison1, Ruoxin Li1, Asif Alam1, Anastasia Adrahtas1, Elizabeth M Algar2, Zane S Kaplan3.
1 Thalassaemia & Haemophilia Molecular Reference Laboratory, Level 3 Monash Medical Centre 246 Clayton Road, CLAYTON, VIC, 3168, firstname.lastname@example.org
2 Genetics and Molecular Pathology, Level 3 Monash Medical Centre 246 Clayton Road, CLAYTON, VIC, 3168
3 Medical Therapy Unit, Level 2 Monash Medical Centre 246 Clayton Road, CLAYTON, VIC, 3168
Haemophilia A is a recessive X-linked disorder caused by mutations of the Factor VIII gene (F8) that lead to a reduction in the amount of factor VIII protein produced. Factor VIII protein is involved in the blood coagulation pathway, with phenotypes classified according to the factor VIII activity ranging from mild (>5%), moderate (1-5%), to severe (<1%). Reported mutations in F8 include single base substitutions, small indels, and inversions affecting intron 22 and intron 1. Less frequently observed are large deletions and duplications of various lengths in the gene. With the wide-spread adoption of additional molecular techniques, such as multiplex ligation-dependent probe amplification (MLPA), novel mutations in F8 are being discovered.
An affected male in which previous investigations for severe haemophilia A had not detected any substitutions, indels, or inversions was investigated further with MLPA. An unreported duplication of exons 7, 8, and 9 in the F8 was detected. We present here the family affected by this duplication.
Jeremy has been working as a medical scientist with Monash Health since 2011 after graduating from Monash University with a Bachelor of Science (Genetics).