In silico study of correlation between missense variations of F8 gene and inhibitor formation in severe hemophilia A

Fodil, Mostefa; Zemani, Faouzia

doi:10.4274/tjh.galenos.2019.2019.0094

Cited by 1 publication

(2 citation statements)

References 40 publications

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“…Moreover, a case of missense mutation was associated with a severe phenotype of hemophilia A and developed inhibitors. While many authors associate missense mutations with a low risk of inhibitor occurrence [19], Fodil et al reported a frequency of 13.51% of severe hemophilia A patients with missense mutations who developed inhibitors in their study [23]. According to their study, the risk of developing anti-FVIII inhibitors increases when the substitution results in an amino acid class change.…”

Section: Discussionmentioning

confidence: 92%

“…Indeed, in the missense mutation found in patient HA 56 during our study, arginine was replaced by histidine at position 2169. According to the amino acid distribution, arginine belongs to class 4 (basic), while histidine is polar, neutral, and belongs to class 2 [23]. Therefore, it is necessary to continue this study on a larger population to better understand these different mechanisms in the Beninese population.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Study of Factor VIII Inhibitor and F8 Gene Mutations in Persons with Hemophilia A from Benin

Baglo,

Zohoun,

Houssou

et al. 2024

IBRR

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Aim: determine the prevalence of a FVIII inhibitors and identify the genetic mutations associated with their development in beninese personne with hemophilia (PwH) A. Study Design: this is cross-sectional descrptive study conducted from June 2022 to May 2023 in hemophilia treatment centers in Benin. Methodology: Inhibitor screening was carried out systematically in all PwHs A receiving FVIII infusion through determination of the circulating anticoagulant index and the Nijmegen-Bethesda assay. The molecular study strategy used for the F8 gene associated with hemophilia A is dependent on the severity of the hemophilia. Other data were collected either from patients' responses to the questionnaire or by studying their medical records and the center's hemophilia registry. Results: Of the 97 PwHs A followed up, 57 had been treated with FVIII infusion. Of these, 21 had developed inhibitors, representing a frequency of 36.8% of treated PwHs A and 43.75% of severe PwHs. None of the moderate or mild PwHs A had developed anti-FVIII antibodies. PwHs A with inhibitors had a median age of 11 years, ranging from 1 to 66 years. The Nijmegen-Bethesda test revealed 11 high responders and 10 low responders. Mutation analysis of the F8 gene revealed seven cases of intron 22 inversion, seven cases of nonsense mutations, three cases of deletion and one case of missense mutation. Mutations weren’t identified in three patients because their DNA did not amplify on long-distance PCR. In terms of therapy, immune tolerance induction wasn’t achieved in any of the 21 patients, but they are treated with emicizumab and bypass depending on the context. Conclusion: Although a cross-sectional study with a limited sample size, this study provides valuable information on beninese PwHs A with inhibitors. The frequency of inhibitors is high in treated PwHs A, and almost all patients who have developed inhibitors have high-risk genetic mutations.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%