A de novo factor <scp>VIII</scp> mutation in a haemophilia B family leading to combined deficiency of factor <scp>VIII</scp> and <scp>IX</scp>

Prabhudesai, Aniket; Shanbhag, S.; Mirgal, Darshana; Kawankar, Nikesh; Shetty, Shrimati

doi:10.1111/hae.13307

Cited by 2 publications

(3 citation statements)

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“…Combined factor deficiencies are likely underestimated, and comprehensive coagulation testing is recommended for all patients and siblings for accurate diagnosis and treatment 3 . Patients with HA and HB need FVIII and FIX replacement.…”

Section: Resultsmentioning

confidence: 99%

“…Congenital hemophilia A (HA) and B (HB) are rare X‐linked recessive disorders, occurring in approximately 1 in 5000 and 1 in 30 000 live male births, respectively 1 . Combined inheritance of HA and HB is even more rare, but has been reported due to inheritance of 1 variant from each parent 2 or due to 2 variants from a single parent 3‐6 . We report 2 families with pathogenic genetic variants for HA and HB and evaluate how the variant F8 and F9 alleles were inherited within the families.…”

Section: Introductionmentioning

confidence: 99%

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The odds and implications of coinheritance of hemophilia A and B

Karch

Masser-Frye

Limjoco

et al. 2020

Research and Practice in Thrombosis and Haemostasis

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We report 2 patients with coinheritance of the X‐linked bleeding disorders hemophilia A and hemophilia B. We describe the family pedigrees, clinical features, and genotyping. The case report addresses the key clinical questions of how to manage patients with both hemophilia A and B and how to counsel families regarding recurrence risk. The patients with coinherited hemophilia A and B require a combination of factor VIII and factor IX replacement to achieve hemostasis. We calculated the estimated genomic meiotic recombination frequency between F8 and F9 to be 38%. The findings in these cases are consistent with this calculation. These findings provide critical information for management of families with coinherited hemophilia A and B.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The odds and implications of coinheritance of hemophilia A and B

Karch

Masser-Frye

Limjoco

et al. 2020

Research and Practice in Thrombosis and Haemostasis

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“…Causative gene defects can be classified into genetic variants affecting protein biosynthesis/secretion, resulting in low antigen or activity in plasma, or genetic alterations leading to the secretion of a dysfunctional protein. In FMCFDs arising from the coincidental concomitant inheritance of separate coagulation-factor deficiencies, a combination of different disease-causing genetic changes in affected factors can be detected [ 17 , 18 , 19 ]. In FMCFDs arising from a single-gene defect, such as combined FV and FVIII deficiency and combined deficiency of the vitamin K–dependent factors, genetic variants in the genes encoding proteins responsible for the intracellular trafficking of FV and FVIII, (multiple coagulation factor deficiency 2 ( MCFD2 ) and lectin mannose-binding 1 ( LMAN1 )) and genetic variants in genes encoding enzymes involved in post-translational modification and vitamin K metabolism (γ-glutamylcarboxylase ( GGCX ) and vitamin K epoxide reductase complex subunit 1 ( VKORC1 )) are reported [ 7 , 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Familial Multiple Coagulation Factor Deficiencies (FMCFDs) in a Large Cohort of Patients—A Single-Center Experience in Genetic Diagnosis

Preisler¹,

Pezeshkpoor²,

Banchev

et al. 2021

JCM

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Background: Familial multiple coagulation factor deficiencies (FMCFDs) are a group of inherited hemostatic disorders with the simultaneous reduction of plasma activity of at least two coagulation factors. As consequence, the type and severity of symptoms and the management of bleeding/thrombotic episodes vary among patients. The aim of this study was to identify the underlying genetic defect in patients with FMCFDs. Methods: Activity levels were collected from the largest cohort of laboratory-diagnosed FMCFD patients described so far. Genetic analysis was performed using next-generation sequencing. Results: In total, 52 FMCFDs resulted from coincidental co-inheritance of single-factor deficiencies. All coagulation factors (except factor XII (FXII)) were involved in different combinations. Factor VII (FVII) deficiency showed the highest prevalence. The second group summarized 21 patients with FMCFDs due to a single-gene defect resulting in combined FV/FVIII deficiency or vitamin K–dependent coagulation factor deficiency. In the third group, nine patients with a combined deficiency of FVII and FX caused by the partial deletion of chromosome 13 were identified. The majority of patients exhibited bleeding symptoms while thrombotic events were uncommon. Conclusions: FMCFDs are heritable abnormalities of hemostasis with a very low population frequency rendering them orphan diseases. A combination of comprehensive screening of residual activities and molecular genetic analysis could avoid under- and misdiagnosis.

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A de novo factor VIII mutation in a haemophilia B family leading to combined deficiency of factor VIII and IX

Cited by 2 publications

References 10 publications

The odds and implications of coinheritance of hemophilia A and B

The odds and implications of coinheritance of hemophilia A and B

Familial Multiple Coagulation Factor Deficiencies (FMCFDs) in a Large Cohort of Patients—A Single-Center Experience in Genetic Diagnosis

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