Recurrent and novel disease‐causing <i>F8</i> variants in boys with severe haemophilia A in Poland

Janczar, Szymon; Bąbol-Pokora, Katarzyna; Jatczak‐Pawlik, Izabela; Wypyszczak, Kamila; Klukowska, Anna; Łaguna, Paweł; Kostrzewska, Magdalena; Wegner, Olga; Zieliński, J J; Kołtan, Andrzej; Bobrowska, Halina; Woznica-Karczmarz, Irena; Dakowicz, Lucja; Włazłowski, Marek; Rurańska, Iwona; Dobaczewski, Grzegorz; Radwańska, Monika; Karolczyk, Grażyna; Pietrys, Danuta; Balwierz, Walentyna; Szczepański, Tomasz; Urasiński, Tomasz; Płoski, Rafał; Młynarski, Wojciech

doi:10.1111/hae.13784

Cited by 2 publications

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References 10 publications

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“…No phenotypic data is available. The details of the dataset are available in our previous publication [10].…”

Section: Polish Reference Populationmentioning

confidence: 99%

“…F8 intron 22 and intron 1 inversion assays with Inverse shiftingpolymerase chain reaction (IS-PCR) were all conducted as previously described in our study of 101 Polish boys with hemophilia A [10] according to a slight modification of an inverse shifting-polymerase chain reaction (IS-PCR) described originally by Rossetti et al [11]. 2 μg of genomic DNA was digested with 20 units of BclI (ThermoFisher Scientific, USA) at 55°C over 4 h in 50 ul.…”

Section: F8 Intron 22 and Intron 1 Inversion Assays -Inverse Shifting-polymerase Chain Reaction (Is-pcr)mentioning

confidence: 99%

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Six molecular patterns leading to hemophilia A phenotype in 18 females from Poland

Janczar

Bąbol-Pokora

Jatczak‐Pawlik

et al. 2020

Thrombosis Research

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Introduction: Female hemophilia is an intriguing rare disorder and few larger reports on its genetic etiology are available. While historically the diagnosis was satisfactorily reached by factor VIII activity assays, the clinical and potentially therapeutic heterogeneity of female hemophilia calls for comprehensive molecular diagnosis in each case. Currently, the genetic investigations are not a part of routine, state-funded, diagnostics in Poland, and thus molecular epidemiological data are missing. Aim: We set out to perform a comprehensive genetic analysis of Polish females with hemophilia A. Patients/methods: Eighteen females with hemophilia A (including 2 with severe and 5 with moderate hemophilia phenotype) consented for genetic diagnostics. To establish F8 mutations, we used next-generation sequencing of a panel of genes associated with hematological disorders, standard assays for recurrent intragenic F8 inversions and MLPA when deletions were suspected. When appropriate we also used karyotyping, genomic microarrays and X chromosome inactivation assays. Results: While abnormally skewed X-chromosome inactivation combined with a F8 variant on the active allele was, as expected, the most common genetic etiology, a number of other genetic scenarios were unraveled. This included: misdiagnosis (molecular diagnosis of vWd), Turner syndrome, compound heterozygosity and androgen insensitivity syndrome (a phenotypical 46,XY female with a novel androgen receptor gene mutation). We report 3 novel F8 mutations. Conclusion: Every case of female hemophilia warrants full genomic diagnostics, as this may change the diagnosis or reveal broader morbidity than a coagulation disorder (Turner syndrome, androgen insensitivity, or cardiovascular morbidity that we described previously in a SHAM syndrome carrier).

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“…No phenotypic data is available. The details of the dataset are available in our previous publication [10].…”

Section: Polish Reference Populationmentioning

confidence: 99%

Section: F8 Intron 22 and Intron 1 Inversion Assays -Inverse Shifting-polymerase Chain Reaction (Is-pcr)mentioning

confidence: 99%

Six molecular patterns leading to hemophilia A phenotype in 18 females from Poland

Janczar

Bąbol-Pokora

Jatczak‐Pawlik

et al. 2020

Thrombosis Research

Self Cite

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HL-A11:01, -B51:01, -DQB102:02 and -DRB107:01 are associated with inhibitor development in boys with severe haemophilia A receiving rFVIII prophylaxis in Poland

Janczar

Tymoniuk

Ming

et al. 2021

Thrombosis Research

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Recurrent and novel disease‐causing F8 variants in boys with severe haemophilia A in Poland

Cited by 2 publications

References 10 publications

Six molecular patterns leading to hemophilia A phenotype in 18 females from Poland

Six molecular patterns leading to hemophilia A phenotype in 18 females from Poland

HL-A11:01, -B51:01, -DQB102:02 and -DRB107:01 are associated with inhibitor development in boys with severe haemophilia A receiving rFVIII prophylaxis in Poland

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Recurrent and novel disease‐causing F8 variants in boys with severe haemophilia A in Poland

Cited by 2 publications

References 10 publications

Six molecular patterns leading to hemophilia A phenotype in 18 females from Poland

Six molecular patterns leading to hemophilia A phenotype in 18 females from Poland

HL-A*11:01, -B*51:01, -DQB1*02:02 and -DRB1*07:01 are associated with inhibitor development in boys with severe haemophilia A receiving rFVIII prophylaxis in Poland

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HL-A11:01, -B51:01, -DQB102:02 and -DRB107:01 are associated with inhibitor development in boys with severe haemophilia A receiving rFVIII prophylaxis in Poland