Identification of deep intronic variants in 15 haemophilia A patients by next generation sequencing of the whole factor VIII gene.

摘要: Current screening methods for factor VIII gene (F8) mutations can reveal the causative alteration in vast majority of haemophilia A patients. Yet, standard diagnostic fail about 2 % cases. This study aimed at analysing entire intronic sequences F8 15 patients by next generation sequencing. All had a mild to moderate phenotype and no mutation coding sequence splice sites could be diagnosed so far. Next sequencing data revealed 23 deep candidate variants several introns, including six recurrent three that have been described before. One patient additionally showed deletion 9.2 kb intron 1, mediated Alu-type repeats. Several bioinformatic tools were used score comparison known pathogenic order predict their deleteriousness. Pedigree analyses correct segregation pattern presumptive mutations. In each analysed, least one variant was identified predicted alter mRNA splicing. Reduced levels and/or stability would well compatible with patients’ phenotypes. The approach proved an efficient method screen complete applied as one-stop molecular diagnostics A.