Associate Researcher Department of Hematology, Zhongnan Hospital of Wuhan University Wuhan, Hubei, China (People's Republic)
Background: Compound heterozygous or homozygous loss-of-function mutations in the F12 gene can lead to FⅫ deficiency, an autosomal recessive genetic disease characterized by reduced FⅫ activity with or without reduced FⅫ antigen levels.
Aims: To analyze the clinical phenotype and genetic testing results of a patient with inherit Factor Ⅻ (FⅫ) deficiency and explore the clinical and molecular biological characteristics of FⅫ deficiency in the Chinese population
Methods: Clinical case data were collected from a proband with inherit FⅫ deficiency, and coagulation function-related laboratory tests and gene analysis were performed on family members.Literature searches were conducted in the published database on FⅫ deficiency in the Chinese population, with the search period up to September 30th, 2023.
Results: The proband was a 37-year-old female parturient, with prenatal examination results indicating APTT exceeding 120 s, and Factor Ⅻ activity (FⅫ:C) and antigen levels (FⅫ:Ag) both at 1%. Gene sequencing revealed F12 gene compound heterozygous mutations, c.303_304del:p.His101Glnfs36 and c.1092dupC:p.Lys365Glnfs69. The proband's father, mother, brother, eldest daughter, second daughter, and son were all carriers of one heterozygous mutation, with varying degrees of reduction in FⅫ:C and FⅫ:Ag. A literature review identified 46 articles reporting a total of 87 cases of FⅫ deficiency in the Chinese population. Among all patients, 42 F12 gene mutations were reported, with missense mutations being the most common (n=23, 52.4%). The catalytic (Peptidase S) domain was the most frequently affected structural domain (n=23, 52.4%). The most frequently detected mutation was c.1681G>A (n=16 cases, 19.3%), followed by c.1561G>A:p.Glu521Lys (n=12, 14.3%).
Conclusion(s): This study reports a case of inherit Factor Ⅻ deficiency with compound heterozygous mutations in the F12 gene, along with familial characteristics. The study summarizes the clinical features and genetic characteristics of inherit FⅫ deficiency in the Chinese population, providing a foundation for future systematic research.
