Molecular Diagnosis of Hemophilia A and Pathogenesis of Novel F8 Variants in Shanxi, China.

The aim of this study was to perform a molecular diagnosis of hemophilia A (HA) among patients in the Shanxi Province of China. Fifty-two HA patients were tested, including IVS22 (31 samples), IVS1 (3 samples), missense (11 samples), nonsense (3 samples), and 4 cases of frameshift (2 cases of deletion, 1 case of insertion, 1 case of single-base duplication). With the exception of the single-base G duplication variant (p.Ile1213Asnfs28), this was the hotspot variant reported by research groups at an early stage. The remaining variants were found, for the first time, in the region. The missense variants p.Cys172Ser, p.Tyr404Ser, p.Asp1903Gly, and p.Ser2284Asn, the deletion variant p.Leu2249fs9, and the insertion variant p.Pro2319fs*97 were novel variants. The application of next-generation sequencing (NGS) molecular diagnosis enriched the variant spectrum of HA, which is greatly significant for individualized genetic counseling, clinical diagnosis, and treatment. NGS and a variety of bioinformatics prediction methods can further analyze the impact of genetic variation on protein structure or function and lay the foundation to reveal the molecular pathogenic mechanism of novel variants.