An aberrant 8 intron 1 inversion with concomitant large duplication and deletion in a Chinese severe hemophilia A patient.

Objectives: Hemophilia A (HA, OMIM: 306700) is an X-linked recessive bleeding disorder, caused by defects of the gene which encodes the coagulation factor VIII (FVIII). F8 intron 22 and intron 1 inversion (Inv22 and Inv1) account for ∼45% and 1-5% of severe HA cases, respectively. We herein described an aberrant Inv1 with concomitant large duplication and deletion in a Chinese severe HA patient.

Methods: Long distance PCR and multiplex PCR were used to detect Inv22 and Inv1. Multiplex ligation-dependent probe amplification (MLPA) was applied to examine exonic duplication and deletion of the gene. Coverage analysis of read depth data from whole-genome sequencing (WGS) was used to analyze the intronic duplication and deletion of the gene.

Results: We have identified an aberrant F8 Inv1 in a 1-year-old Chinese severe HA patient showing inversed int1h-1 and normal int1h-2. Coverage analysis of WGS data further illustrated the aberrant Inv1 with concomitant a duplication of 117 kb and a deletion of 1.8 kb.

Conclusion: In conclusion, we reported an aberrant Inv1 with concomitant large duplication and deletion in a severe Chinese HA patient. Moreover, WGS provides rapid genetic diagnosis of hereditary disorders with point mutations, deletions, insertions and CNVs.