A novel missense mutation in F9 gene causes hemophilia B in a family with clinical variability

Y, Seo; Yang, Qi; Zuo, Yangjin; Li, Mengting; Luo, Jingsi; Qin, Zailong; Zhang, Qinle; Li, Meng; Huang, Limei; Lu, Yingchi; Feng, Shihan; Fan, Xin

doi:10.1097/mbc.0000000000000884

Cited by 4 publications

(2 citation statements)

References 19 publications

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“…The F9 gene (Xq27.1-q2.2) is approximately 33.5 kb in length and contains eight exons [ 6 , 9 ]. FIX is homologous to clotting factors VII (FVII) and XI (FXI).…”

Section: Introductionmentioning

confidence: 99%

Mutation analysis and characterisation of F9 gene in haemophilia- B population of India

Kulkarni

Hegde²,

Hegde³

et al. 2021

Blood Res

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Background: Hemophilia B (HB) is an X-linked bleeding disorder resulting from coagulation factor IX (FIX) defects. Over 3,000 pathogenic, HB-associated mutations in the F9 gene have been identified. We aimed to investigate the role of F9 variants in 150 HB patients using sequencing technology.Methods: F9 gene sequences were amplified from peripheral blood-derived DNA and sequenced on an Applied Biosystems (ABI) 3500 Sanger sequencing platform. Functional and structural predictions of mutant FIX were analyzed.Results: Among 150 HB patients, 102 (68%), 30 (20%), and 18 (12%) suffered from severe, moderate, and mild HB, respectively. Genetic analysis identified 16 mutations, including 3 novel mutations. Nine mutations (7 missense and 2 stop-gain) were found to be pathogenic. Only 3 mutations (c.127C>T, c.470G>A, and c.1070G>A) were associated with different severities. While 2 mutations were associated with mild HB cases (c.304C>T and c.580A>G), 2 (c.195G>A and c.1385A>G) and 3 mutations (c.223C>T, c.1187G>A, and c.1232G>A) resulted in moderate and severe disease, respectively.Additionally, 1 mutation each was associated with mild-moderate (c.*1110A>G) and mild-severe HB disease (c.197A>T), 4 mutations were associated with moderate-severe HB cases (c.314A>G, c.198A>T, c.676C>T, and c.1094C>A). FIX concentrations were lower in the mutated group (5.5±2.5% vs. 8.0±2.5%). Novel p.E66D and p.S365 mutations were predicted to be pathogenic based on changes in FIX structure and function. Conclusion:Novel single nucleotide polymorphisms (SNPs) largely contributed to the pathogenesis of HB. Our study strongly suggests that population-based genetic screening will be particularly helpful to identify risk prediction and carrier detection tools for Indian HB patients.

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“…The F9 gene (Xq27.1-q2.2) is approximately 33.5 kb in length and contains eight exons [ 6 , 9 ]. FIX is homologous to clotting factors VII (FVII) and XI (FXI).…”

Section: Introductionmentioning

confidence: 99%

Mutation analysis and characterisation of F9 gene in haemophilia- B population of India

Kulkarni

Hegde²,

Hegde³

et al. 2021

Blood Res

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show abstract

“…PCR is used for common variants (32) and sequencing for rare variants. The F9 gene sequencing can be performed through Sanger sequencing (33) or next generation sequencing (NGS) technologies (34). Genetic counseling for prospective parents before conception is important.…”

Section: Figurementioning

confidence: 99%

Current therapeutic approaches in the management of hemophilia—a consensus view by the Romanian Society of Hematology

et al. 2021

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Hemophilia A (HA) and hemophilia B (HB) are rare disorders, being caused by the total lack or under-expression of two factors from the coagulation cascade coded by genes of the X chromosome. Thus, in hemophilic patients, the blood does not clot properly. This results in spontaneous bleeding episodes after an injury or surgical intervention. A patient-centered regimen is considered optimal. Age, pharmacokinetics, bleeding phenotype, joint status, adherence, physical activity, personal goals are all factors that should be considered when individualizing therapy. In the past 10 years, many innovations in the diagnostic and treatment options were presented as being either approved or in development, thus helping clinicians to improve the standard-of-care for patients with hemophilia. Recombinant factors still remain the standard of care in hemophilia, however they pose a challenge to treatment adherence because they have short halflife, which where the extended half-life (EHL) factors come with the solution, increasing the half-life to 96 hours. Gene therapies have a promising future with proven beneficial effects in clinical trials. We present and critically analyze in the current manuscript the pros and cons of all the major discoveries in the diagnosis and treatment of HA and HB, as well as identify key areas of hemophilia research where improvements are needed.

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Genotype-phenotype analyses of Iranian patients with hemophilia B (Leyden -) and hemophilia B (Leyden +): A single-center study

Moghadam,

Manafzadeh,

Dajliry

et al. 2024

Transfusion and Apheresis Science

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A novel missense mutation in F9 gene causes hemophilia B in a family with clinical variability

Cited by 4 publications

References 19 publications

Mutation analysis and characterisation of F9 gene in haemophilia- B population of India

Mutation analysis and characterisation of F9 gene in haemophilia- B population of India

Current therapeutic approaches in the management of hemophilia—a consensus view by the Romanian Society of Hematology

Genotype-phenotype analyses of Iranian patients with hemophilia B (Leyden -) and hemophilia B (Leyden +): A single-center study

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