An aberrant F8 intron 1 inversion with concomitant large duplication and deletion in a Chinese severe hemophilia A patient.

Abstract:

OBJECTIVES:Hemophilia A (HA, OMIM: 306700) is an X-linked recessive bleeding disorder, caused by defects of the F8 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 F8 gene. Coverage analysis of read depth data from whole-genome sequencing (WGS) was used to analyze the intronic duplication and deletion of the F8 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.

journal_name

Hematology

authors

Wang X,Wang H,Tan H,Liu XP,Li H

doi

10.1080/16078454.2020.1867793

subject

Has Abstract

pub_date

2021-12-01 00:00:00

pages

53-57

issue

1

eissn

1024-5332

issn

1607-8454

journal_volume

26

pub_type

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