The Clinical Genetics of Hemophilia B (Factor IX Deficiency)

Miller, Connie H.

doi:10.2147/tacg.s288256

Cited by 13 publications

(10 citation statements)

References 77 publications

(101 reference statements)

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“…Female hemophilia carriers can be classified as obligate (daughters of affected male, women with > 1 affected son, women with 1 affected son and an affected brother or uncle) or possible (women with 1 affected son and no family history, daughters of an obligate carrier and woman with a maternal family history of hemophilia). A de novo germ cell X chromosome mutation is found in 30%–50% of newborn boys with hemophilia 21 – 26 , 45 – 47 ( Table 1 ).…”

Section: Common Etiologies and Diagnoses Identified In Females With I...mentioning

confidence: 99%

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Preoperative diagnosis and management of inherited bleeding disorders in female adolescents and adults

Wilson

2023

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Although inherited bleeding disorders (IBDs) affect both females and males, this review of the preoperative diagnosis and management of IBDs focuses on genetic and gynecologic screening, diagnosis and management of affected and carrier females. A PubMed literature search was conducted, and the peer-reviewed literature on IBDs was evaluated and summarized. Best-practice considerations for screening, diagnosis and management of IBDs in female adolescents and adults, with GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) evidence level and ranking of recommendation strength, are presented. Health care providers need to increase their recognition of and support for female adolescents and adults with IBDs. Improved access to counselling, screening, testing and hemostatic management is also required. Patients should be educated and encouraged to report abnormal bleeding symptoms to their health care provider when they have a concern. It is hoped that this review of preoperative IBD diagnosis and management will enhance access to women-centred care to increase patients’ understanding of IBDs and decrease their risk of IBD-related morbidity and mortality.

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Section: Common Etiologies and Diagnoses Identified In Females With I...mentioning

confidence: 99%

“…Genetic mechanisms explain most of the reported clinical variability. Possible causes of FVIII and FIX deficiency in women and girls are 23 , 26 , 48 – 51 …”

Section: Common Etiologies and Diagnoses Identified In Females With I...mentioning

confidence: 99%

Preoperative diagnosis and management of inherited bleeding disorders in female adolescents and adults

Wilson

2023

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“…With the use of molecular genetic linkage analysis, F9 was identified as the pathogenic gene of hemophilia B. The FIX gene spans 34 kb on the long arm of X chromosome at band Xq27.1 and consists of eight exons and seven introns [ 12 , 13 ] ( Figure 1 ). The eight exons transcribe into a 2.8 kb mRNA (NM_000133) with a 1.4 kb noncoding region at the 3′ end [ 14 ].…”

Section: The Gene Of Fixmentioning

confidence: 99%

The Molecular Basis of FIX Deficiency in Hemophilia B

Shen

Gao

Cao

et al. 2022

IJMS

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Coagulation factor IX (FIX) is a vitamin K dependent protein and its deficiency causes hemophilia B, an X-linked recessive bleeding disorder. More than 1000 mutations in the F9 gene have been identified in hemophilia B patients. Here, we systematically summarize the structural and functional characteristics of FIX and the pathogenic mechanisms of the mutations that have been identified to date. The mechanisms of FIX deficiency are diverse in these mutations. Deletions, insertions, duplications, and indels generally lead to severe hemophilia B. Those in the exon regions generate either frame shift or inframe mutations, and those in the introns usually cause aberrant splicing. Regarding point mutations, the bleeding phenotypes vary from severe to mild in hemophilia B patients. Generally speaking, point mutations in the F9 promoter region result in hemophilia B Leyden, and those in the introns cause aberrant splicing. Point mutations in the coding sequence can be missense, nonsense, or silent mutations. Nonsense mutations generate truncated FIX that usually loses function, causing severe hemophilia B. Silent mutations may lead to aberrant splicing or affect FIX translation. The mechanisms of missense mutation, however, have not been fully understood. They lead to FIX deficiency, often by affecting FIX’s translation, protein folding, protein stability, posttranslational modifications, activation to FIXa, or the ability to form functional Xase complex. Understanding the molecular mechanisms of FIX deficiency will provide significant insight for patient diagnosis and treatment.

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“…In most cases, the carrier females may have increased bleeding during menstruation and after delivery [ 17 ], & [ 12 ]. In neonates with intracranial hemorrhage or bleeding post circumcision, hemophilia is suspected, and clear female sex does not exclude the disease [ 18 ], & [ 13 ]. Carriers with lowered clotting factor levels, especially pregnant carriers, may have a higher risk of postpartum bleeding [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Investigation of the Bleeding Tendency in Sudanese Female Carriers of Hemophilia B

Abker

Elzaki

Elmahdi

et al. 2022

BioMed Research International

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Background. Hemophilia (HB) is an X-linked, recessive bleeding disorder characterized by the deficiency or absence of the coagulation factor IX. Usually, females are carriers of the trait, while males are affected. FIX deficiency leads to uncontrollable bleeding events, and the severity is dependent on the levels of the clotting factor. The objective of this research was to measure the prevalence of bleeding tendency in Sudanese carriers of HB. Materials and Methods. In this cross-sectional study, 88 Sudanese carriers of HB participated. The activated partial thromboplastin time test (APTT) and FIX test were performed for each carrier. The frequencies of DNA polymorphism and FIX-linked restriction fragments BamHI, HhaI, and MnII were also assessed. The study was conducted in Khartoum, Sudan, during the period from 2015 to 2017. Results. The study showed that 55 (62.5%) HB carriers were from the Laban village in the White Nile State, and all of them were members of the Shinkheb tribe. The mean age of the study population was 26.3 years. Among the carriers, 57 (64.7%) had abnormal coagulation profiles. The mean value of the APTT level among carriers was significantly increased ( P value: 0.000), while the mean concentration of the FIX levels among the carriers was significantly decreased ( P value: 0.000). The study also showed a negative correlation between PTT and F assay with P value of 0.000 and R value of 0.578. Conclusion. The APTT is high in most carriers and the FIX assay level is low in most carriers. Most carriers had no symptoms and were not bleeding. The Shinkheb tribe is the most ethnic tribe carrying HB (62.5%). HhaII is more informative for carrier detection than others, but it is of significant value if both (MnII and HhaII) were performed in parallel. In Sudanese, BamHI was informative but MnII and HhaII were best in the mutation detection and for prenatal diagnosis.

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The Clinical Genetics of Hemophilia B (Factor IX Deficiency)

Cited by 13 publications

References 77 publications

Preoperative diagnosis and management of inherited bleeding disorders in female adolescents and adults

Preoperative diagnosis and management of inherited bleeding disorders in female adolescents and adults

The Molecular Basis of FIX Deficiency in Hemophilia B

Investigation of the Bleeding Tendency in Sudanese Female Carriers of Hemophilia B

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