Large duplications within the FVIII gene contribute to mutation spectrum of haemophilia A

Haemophilia A is caused by a variety of mutations in the FVIII gene: missense and nonsense mutations, small and large deletions and insertions, as well as sub-chromosomal inversions. So far, only one duplication of a whole exon of the FVIII gene, exon 13, has been published by an Italian working group. Duplications comprising whole exons are difficult to detect by current routine methods for mutation screening in X-chromosomal disorders. We have applied multiplex ligation-dependent probe amplification (MLPA) – a recent technique for the quantitative analysis of gene copy numbers – to the FVIII gene.