Mutation spectrum of F8, F9 gene in Mongolian patients with Hemophilia A, B
- VernacularTitle:Монголд оношлогдсон Гемофили А, Б өвчний зарим тохиолдлуудад F8, F9 генийн мутацийг илрүүлсэн дүн
- Author:
Purevdorj M
1
;
Purevdorj I
1
;
Munkhtsetseg B
1
;
Tungalagtamir T
1
;
Sodnomtsogt L
2
;
Mannhalter Ch
3
;
Erkhembulgan P
1
;
4
Author Information
1. Department of Molecular Biology and Genetics, School of Bio-medicine, MNUMS, Ulaanbaatar, Mongolia
2. Institute of Neuroscience and Psychology, Mongolian Academy of Sciences, Ulaanbaatar, Mongolia
3. Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
4. Health Department of Ulaanbaatar
- Publication Type:Journal Article
- Keywords:
Hemophilia A;
Hemophilia B;
F8;
F9;
Mongolia;
mutation
- From:
Mongolian Journal of Health Sciences
2026;92(2):67-72
- CountryMongolia
- Language:Mongolian
-
Abstract:
Background:Identifying pathogenic variants in the F8, F9 gene in patients with hemophilia A (HA) and Hemophilia B (HB) is crucial for improving genetic counseling, understanding genotype–phenotype correlations, assessing inhibitor risk, and establishing family-specific mutation profiles.
Aim:To detect mutations in the F8 and F9 genes among people with hemophilia A and B diagnosed in Mongolia.
Materials and Methods:Long-distance PCR were used to detect intron-22 and intron-1 inversions. Sanger sequencing identified nucleotide substitutions, deletion, and insertion in F8 and F9 gene.
Result:Thirty-two male patients with HA (30 severe, one moderate, and one mild) from 27 unrelated families, eight patients with Hemophilia B were analyzed. Among 25 families with severe HA, pathogenic variants were found in 24 families (95.6%). Large structural rearrangements were detected in 22 patients from 19 families, including intron-22 inversion in 16 cases of 14 families, intron-1 inversion in four cases from three families, and two large deletions found in two unrelated families. In one severe case, no pathogenic variant was identified in the entire F8 gene. Small scale changes were identified in the remaining patients, including missense in three families and two frameshift variants, all associated with severe phenotype. We found novel c.2240del variant and classified as pathogenic. A known polymorphism (c.3864A>C) was identified in one patient with moderate HA, while a novel intronic deletion (c.1010-106delA) was detected in a patient with mild disease. Two families had a history of HB. A total of five different variants (c.223C>T; c.344A>G; c.464G>C; c.187_188del; and c.1314_1314delA) were identified in six patients with severe HB. Of these, two (c.187_188del and c.1314_1314delA) were novel. No variant in the entire F9 was found in two patients with mild HB. Nonsense c.223C>T (p.Arg75*) mutation was detected in two unrelated patients.
Conclusion:Intron-22 (56%) and intron-1 (12%) inversions were detected in families with severe HA. A novel c.2240del variant was also identified in association with a severe phenotype. The novel variants c.187_188del and c.1314_1314delA of F9 can cause severe Hemophilia B.
- Full text:20260926205130912512.pdf
