Prenatal diagnosis and genetic analysis of novel missense mutation in FVIII gene.

Abstract

Hemophilia A (HA) is an X-linked recessive hereditary bleeding disorder characterized by recurrent bleeding into muscles, deep tissues, and joint cavities, which may result in varying degrees of disability. Currently, there is no cure for this disease. In this study, the First Hospital of Lanzhou University conducted prenatal diagnosis and family genetic testing on a female carrier of the coagulation factor VIII (FVIII) gene mutation c.5878 C>G in exon 18, classified as a variant of unknown significance. The analysis confirmed that the c.5878 C>G mutation is the pathogenic mutation in the HA family. The proband and her mother were both heterozygous carriers, while her brother was a hemizygous patient. This mutation has not been previously reported and represents a novel pathogenic missense mutation. Family genetic analysis supported the X-linked recessive inheritance pattern. By performing preimplantation genetic testing for monogenic diseases (PGT-M), embryos were screened for the mutation, allowing the carrier to successfully give birth to a healthy child. Screening for FVIII gene mutations to identify mutation types and loci, combined with preconception, preimplantation, and prenatal genetic diagnosis, is critical for reducing adverse pregnancy outcomes and preventing the birth of HA-affected offspring.