Open AccessGenomic alterations in the F8 gene correlating with severe hemophilia A in Egyptian patients
Author(s) -
Mosaad Rehab M.,
Amr Khalda S.,
Rabie Eman A.,
Mostafa Naglaa O.,
Habib Sonia A.,
ElKamah Ghada Y.
Publication year - 2021
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1575
Subject(s) - exon , frameshift mutation , genetics , intron , exome sequencing , nonsense mutation , gene , biology , microbiology and biotechnology , sanger sequencing , exome , phenotype , mutation , dna sequencing , missense mutation
Background Hemophilia A (HA) is an inherited X‐linked recessive coagulation disorder caused by factor VIII ( F8 ) deficiency. F8 rearrangements involving intron 22 (int22) and intron 1 (int1) account for almost half of severe HA phenotype also a hotspot exon 14 provides numerous mutational patterns. This study aims to identify F8 gene mutations among Egyptian HA patients. Methods DNA samples from 60 HA patients were screened for int22 and int1 rearrangements using simplified inverse shifting PCR (IS‐PCR) followed by exon 14 sequencing. Also, four uncharacterized patients were studied by targeted exome sequencing. Results In 33.3% of the studied patients, we identified three int22 rearrangements, three exon 14 mutations (two frameshift; one novel (NM_000132.3:c.2734_2735delAA, p.(N912Ffs*6)), a second reported mutation (NM_000132.3:c.3091_3094delAGAA, p.(K1031Lfs*9)), and one nonsense mutation (NM_000132.3:c.2440C>T, p.(R814*)). All identified mutations were detected in patients with severe HA phenotype. Targeted exome sequencing could not detect any known pathogenic variants. Conclusion Intron 22 rearrangement and exon 14 mutations correlate with most severe hemophilia A Egyptian patients.