Two new mutations affecting the production of functional clotting factor VIII were identified in a group of Vietnamese patients with hemophilia A, researchers report.
Their findings were described in a letter to the editor, “Mutation characteristic of 103 haemophilia A patients in Vietnam: Identification of novel mutations,” published in Haemophilia, the official journal of the World Federation of Hemophilia.
Researchers conducted a genetic analysis on a group of 103 Vietnamese patients with hemophilia A.
Most of the patients (79%) had severe hemophilia, while 22 had the mild to moderate form of the disease. The team could identify disease-causing mutations in the F8 gene, which provides instructions for making the clotting factor VIII (FVIII) in 89% of the patients, which included a total of 55 different gene variants.
Among the identified mutations, the team detected genetic inversions affecting one particular portion of the F8 gene in 35 patients (34%), while the remaining 57 patients had genetic deletions, formation of splicing sites, or nonsense, missense, and frameshift mutations.
Genetic inversion in intron 22 of F8 gene “is reported to be the most common cause of hemophilia A in severe cases, affecting approximately 40%‐50% of the cases,” the researchers wrote. Still, “the study has identified a large spectrum of mutations in the cohort beside the common intron 22 inversion,” they added.
Of the 81 patients with severe hemophilia, 18 (22.22%) were positive for FVIII inhibitors. Within this group, most of the patients had genetic inversions, or had F8 large deletions or nonsense mutations.
The genetic analysis also revealed two new F8 mutations that had not been previously described in the literature. They consisted of the insertion of small portions of genetic code in the F8 sequence, which the team identified as c.4550‐4551insA and c.1268‐1269insG.
The c.1268‐1269insG mutation leads to a frameshift mutation that will cause early termination of the coding sequences, and consequently shorter FVIII protein. The patient who carried this mutation had a severe form of the disease, which is consistent with the biologic impact of the F8 mutation.
“Before the availability of F8 mutation test in Vietnam, criteria for the diagnosis of hemophilia A were solely based on clinical presentations and laboratory tests. This could lead to the under‐diagnosis of hemophilia A, thus overlooking of patients with the milder form of the disease,” the researchers said.
They believe that by adding genetic testing to the assessment of these patients, it will become possible to provide better care and adequate genetic counseling to them.
“The results of this study are adding to the global knowledge base for hemophilia A and thus will promote better awareness for molecular diagnosis and care for hemophilia A patients in Vietnam in the future,” they concluded.