Genetic analysis of carrier status in female members of Japanese hemophilia families

Shinozawa, Keiko; Amano, Kagehiro; Hagiwara, Takeshi; Bingo, Masato; Chikasawa, Yushi; Inaba, Hiroshi; Kinai, Ei; Fukutake, Katsuyuki

doi:10.1111/jth.15301

Cited by 5 publications

(6 citation statements)

References 31 publications

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“…This phenomenon has also been observed in some hemophilia A carriers with normal factor VIII levels as in this case and requires further investigation (Tables S1 and S2) [32,[37][38][39]. Shinozawa et al (2021) mention the impact of age and blood group on FVIII:C level [4]. Biguzzi et al (2021) reported that VWF:Ag and FVIII:C increase with age [40].…”

Section: Genetic Analysis Of F8 Genesupporting

confidence: 61%

“…Despite the clear advantage of nextgeneration sequencing in various settings, Sanger sequencing remains a better option for genetic testing and diagnosis of hemophilia carriers. There may still be a variety of unknown mutations of F8 and F9 target genes as our research and Shinozawa et al (2021) reported [4]. Any new variation found by NGS must still be validated by Sanger sequencing.…”

Section: Genetic Analysis Of F8 Genementioning

confidence: 63%

“…Hemophilia A (HA), hemophilia B (HB), and von Willebrand Disease (VWD) are the most common IBDs associated with a lack of clotting factors (blood coagulation factor VIII (F8), factor IX (F9), and von Willebrand factor (VWF), respectively). Although they are rare diseases, their correct diagnosis is an important component of clinical management as it may inform treatment decisions and carrier status [3,4].…”

Section: Introductionmentioning

confidence: 99%

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Genetic and Bioinformatic Strategies to Improve Diagnosis in Three Inherited Bleeding Disorders in Bogotá, Colombia

Lago

Groot

Navas

et al. 2021

Genes

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Inherited bleeding disorders (IBDs) are the most frequent congenital diseases in the Colombian population; three of them are hemophilia A (HA), hemophilia B (HB), and von Willebrand Disease (VWD). Currently, diagnosis relies on multiple clinical laboratory assays to assign a phenotype. Due to the lack of accessibility to these tests, patients can receive an incomplete diagnosis. In these cases, genetic studies reinforce the clinical diagnosis. The present study characterized the molecular genetic basis of 11 HA, three HB, and five VWD patients by sequencing the F8, F9, or the VWF gene. Twelve variations were found in HA patients, four in HB patients, and 19 in WVD patients. From these variations a total of 25 novel variations were found. Disease-causing variations were used as positive controls for validation of the high-resolution melting (HRM) variant-scanning technique. This approach is a low-cost genetic diagnostic method proposed to be incorporated in developing countries. For the data analysis, we developed an accessible open-source code in Python that improves HRM data analysis with better sensitivity of 95% and without bias when using different HRM equipment and software. Analysis of amplicons with a length greater than 300 bp can be performed by implementing an analysis by denaturation domains.

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Section: Genetic Analysis Of F8 Genesupporting

confidence: 61%

Section: Genetic Analysis Of F8 Genementioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic and Bioinformatic Strategies to Improve Diagnosis in Three Inherited Bleeding Disorders in Bogotá, Colombia

Lago

Groot

Navas

et al. 2021

Genes

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“…We investigated plasma FIX activity and antigen levels in related female carriers 56 , 57 ( n = 3) of the p.R226W variant (Figure 3 ), to explore its potential influence on the proportion of the WT FIX and the inactive FIX variant circulating in plasma. The mean FIXag levels were higher (153.4 ± 18.6%) than the mean FIX activity (78.0 ± 30.3%), which resulted in an activity/antigen ratio decreased to half (0.50 ± 0.15, Figure 3 ), suggesting similarly increased amounts of both FIX molecules.…”

Section: Resultsmentioning

confidence: 99%

F9 missense mutations impairing factor IX activation are associated with pleiotropic plasma phenotypes

Branchini

Morfini

Lunghi

et al. 2022

Journal of Thrombosis and Haemostasis

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“…The gold-standard for diagnosing HB carrier status remains genetic testing. 18 Genetic testing, however, is reserved for individuals with a high suspicion of HB carriership based on family history, aPTT and/or FIX:C levels. How then can HB carriers be identified?…”

Section: Introductionmentioning

confidence: 99%

Identifying hemophilia B carriers: Utility of aPTT, factor IX levels and ratios of factor IX to other Vitamin K dependent factors

Shu,

Malcolmson,

Bosch

et al. 2024

Haemophilia

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IntroductionDiagnosing hemophilia B (HB) carrier status is important to manage bleeding in carriers and to prevent bleeding in potential offspring. Without a family history of hemophilia, diagnosing HB carrier status is challenging. Genetic testing is the gold‐standard, however it is reserved for individuals with a high suspicion of carrier status.AimsTo describe the distribution of activated partial thromboplastin time (aPTT) and factor IX coagulant (FIX:C) levels in HB carriers and assess the ratio of FIX:C to other Vitamin K dependent factors (FII:C, FVII:C, FX:C) as an indicator of HB carrier status.MethodsIn this retrospective, single‐centre cohort study, subjects were included if they were obligate or genetically proven HB carriers. Distributions of aPTT and FIX:C were described and the relationship between FIX:C levels in carriers and severity of familial HB was analysed. Ratios of FIX:C to FII:C, FVII:C, FX:C were calculated.ResultsSeventy‐two female HB carriers (median age: 34 years; IQR 24–43) were included. Median aPTT and FIX:C levels were 33.0 s [IQR 30.0–37.0] and 57 IU/dL [IQR 43–74]. Fifteen carriers (21%) had mild HB (FIX:C levels of 10–40 IU/dL). FIX:C levels trended higher in carriers of mild HB versus carriers of moderate/severe HB. In six carriers, the median ratio of FIX:C to other Vitamin K dependent factors was 0.44, with 92% of ratios being ≤ 0.75.ConclusionaPTT and FIX:C levels were unreliable in diagnosing HB carrier status. A low ratio of FIX:C to other Vitamin K dependent factors may be a useful marker of HB carrier status.

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Genetic analysis of carrier status in female members of Japanese hemophilia families

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 5 publications

References 31 publications

Genetic and Bioinformatic Strategies to Improve Diagnosis in Three Inherited Bleeding Disorders in Bogotá, Colombia

Genetic and Bioinformatic Strategies to Improve Diagnosis in Three Inherited Bleeding Disorders in Bogotá, Colombia

F9 missense mutations impairing factor IX activation are associated with pleiotropic plasma phenotypes

Identifying hemophilia B carriers: Utility of aPTT, factor IX levels and ratios of factor IX to other Vitamin K dependent factors

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