Spectrum of Factor VIII Gene Variants in 78 Patients with Hemophilia A in Guangxi Province, China, Including Nine Novel Variants: A Descriptive Study.

OBJECTIVE

Hemophilia A (HA) is an X-linked hereditary bleeding disorder caused by variants in the coagulation factor VIII (F8) gene, with a current estimated prevalence of 17.1 per 100,000 male individuals. This study aimed to establish a gene variant spectrum in China using long-distance polymerase chain reaction (PCR) and next-generation sequencing.

MATERIALS AND

METHODS

Long-distance PCR was used to detect intron inversions and next-generation sequencing gene panels were used to identify small sequence variants.

RESULTS

Fifty-two different F8 variants were identified in 78 patients from unrelated families, including single-nucleotide alterations (missense, nonsense), frameshifts (small deletions/insertions), splicing-site changes, complex variations, and large rearrangements (inv22 or inv1). The nine variants reported here for the first time include two missense variants, two nonsense variants, four frameshifts, and one splicing alteration.

CONCLUSION

The F8 gene mutation spectrum of patients with HA from Guangxi Province was established and genotype-phenotype correlations were explored. This study contributes data to the existing F8 mutation database and helps systematically identify the mutation spectrum of the gene for HA in southern China.