Background:
Hemophilia A (HA) is an X-linked recessive bleeding disorder with a
high rate of genetic heterogeneity. The present study was conducted on a
large cohort of Iranian HA patients and data obtained from databases.
Methods:
A total of 622 Iranian HA patients from 329 unrelated families who
had been referred to a medical genetics laboratory in Tehran from 2005
to 2019, were enrolled in this retrospective, observational study.
Genetic screening of pathogenic variants of the F8 gene was
performed using inverse shifting PCR, direct sequencing, and multiplex
ligation-dependent amplification (MLPA). Point mutation frequencies in
different exons were analyzed for our samples as well as 6031 HA
patients whose data were recorded in a database.
Results:
A total of 144 different pathogenic or likely pathogenic variants
including 29 novel variants were identified. A strategy to decrease
costs of genetic testing of HA was suggested based on this finding.
Conclusion:
This study provides comprehensive information on F8
pathogenic/likely pathogenic variants in Iranian HA patients which
improves the spectrum of causative mutations and can be helpful to
clinicians and medical geneticists in counseling and molecular diagnosis
of HA.