Factor VIII gene mutations profile in 148 Chinese hemophilia A subjects

Xue, Feng; Zhang, Lei; Sui, Tao; Ge, Junbo; Gu, Dongsheng; Du, Weiting; Zhao, Haifeng; Yang, Renchi

doi:10.1111/j.1600-0609.2010.01481.x

Cited by 25 publications

(21 citation statements)

References 26 publications

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“…A total of 61 patients (61%) had a point mutation detected using direct sequencing analyses. The prevalences of missense mutation and small deletion/insertion mutation were 17% and 23%, respectively, which is comparable with those in previous studies . Nonsense and missense mutations were distributed throughout the whole coding sequences of F8 , whereas frameshift mutations were present mainly in exon 14 (74%, 17/23), a hotspot for such mutations, because of the presence of several long polyadenine runs .…”

Section: Discussionsupporting

confidence: 86%

“…Inv22 mutation accounted for 30% of severe HA patients in this study, which is slightly lower than 45% in severe HA patients from Western countries . Recent studies from Asian countries reported on similar proportions in severe HA patients as in Western countries: 37% (29/79) in a study from Taiwan, 42% (42/100) from Japan and 51% (57/111) from mainland China . Two recent studies involving smaller numbers of HA patients in Korea reported 32% and 40% of Inv22 proportions .…”

Section: Discussioncontrasting

confidence: 42%

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Mutation spectrum and inhibitor risk in 100 Korean patients with severe haemophilia A

et al. 2012

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Summary Haemophilia A (HA) is an X‐linked recessive bleeding disorder caused by defects in the F8 gene encoding the coagulation factor VIII. Mutation analysis in HA is important to confirm the diagnosis, genotype‐phenotype correlations and for genetic counselling and family study. The aim of this study was to detect causative mutations of F8 in severe HA patients in Korea and to correlate the mutation type with the risk of inhibitor development. A total of 100 unrelated Korean patients with severe HA were enrolled for this study. The Nijeman modification of the Bethesda assay was used to determine the presence of inhibitor. Molecular analysis of F8 was performed using a combination of molecular techniques, including long‐distance polymerase chain reaction, direct sequencing and multiplex ligation‐dependent probe amplification (MLPA). We identified causative mutations in 98% of severe HA patients (98/100). Inv22 and Inv1 mutations were detected in 30 patients and one patient, respectively. A total of 59 unique mutations were identified in 69 non‐inversion patients, including 24 novel mutations. The overall prevalence of inhibitor was 26%. Inhibitor risk was highest in patients with large deletion mutations identified using MLPA (100%). Among those with point mutations, the prevalence of inhibitor was highest when the mutation occurred in the A3 and C2 domains (60% and 50%, respectively). The molecular diagnostic strategy involving multiplex PCR, sequencing and dosage analyses identified causative mutations in most cases of severe HA. The high inhibitor risk was associated with large deletion mutations and point mutations in A3 and C2 domains.

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Section: Discussionsupporting

confidence: 86%

Section: Discussioncontrasting

confidence: 42%

Mutation spectrum and inhibitor risk in 100 Korean patients with severe haemophilia A

et al. 2012

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“…We have also found the change of arginine 1781 to histidine in 3 unrelated patients in A3 domain (Faridi et al, 2011). Santacroce et al (2008) were able to detected 384 and 67 (Feng et al, 2010) different mutations and these were mostly effected in the A domains (Table 2).…”

Section: Missense and Nonsense Mutationsmentioning

confidence: 99%

“…These mutations facilitate the dissociation of the A2 subunit, which occurs naturally and inactivates the F8 protein (Hakeos et al, 2002). Phe51Ser, Leu 50Val, Leu197Gln, Met1791Ile and Met1772 Ile were disturbed by the core of A1-A3 domain (Feng et al, 2010;Ma et al, 2008). Between the A1 and A2 domains, residues 351 to 365 are thought to include a binding site for coagulation factor X ) and replacement of Leu50 by a smaller Val side chain create a cavity in the core of A1 and disturb the binding site of FX .…”

Section: Mutations That Affect the A Domainsmentioning

confidence: 99%

Factor VIII genetic mutations and protein alterations in hemophilia A: A review

Faridi¹,

Kumar²,

Husain³

et al. 2014

Clin. Rev. Opinions

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“…Pada ras Cina, Korea, dan Jepang ditemukan defek 22 intron inversion pada pasien hemofilia A berat dengan inhibitor positif berturutturut sebesar 38%, 39,2% dan 42%. 11,12,25 Sedangkan pada ras Saudi Arabia dan Jordania, defek 22 intron inversion ditemukan pada sebagian besar pasien hemofilia A berat, namun penelitian tersebut tidak menghubungkan dengan timbulnya inhibitor. 13,14 3.…”

Section: Derajat Hemofiliaunclassified

Faktor Risiko Timbulnya Inhibitor Faktor VIII pada Anak dengan Hemofilia A

Simatupang

Windiastuti

Oswari

2016

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Latar belakang. Proses timbulnya inhibitor bersifat multifaktorial, baik genetik maupun lingkungan. Beberapa studi telah dilakukan untuk mengetahui faktor risiko terbentuknya inhibitor, namun masih terdapat pendapat yang kontroversial. Di Indonesia, skrining inhibitor tidak rutin dilakukan karena keterbatasan biaya dan alat, sehingga diperlukan suatu penelitian yang dapat dijadikan acuan pemeriksaan inhibitor selektif.Tujuan. Mengetahui prevalensi , karakteristik klinis, dan faktor risiko timbulnya inhibitor pada anak dengan hemofilia A di Departemen IKA- RSCM.Metode. Uji potong lintang dilakukan pada anak usia ≤18 tahun di Pusat Hemofilia Terpadu IKA-RSCM. Analisis bivariat dilakukan dengan uji Fisher. Analisis multivariat tidak dilakukan karena tidak memenuhi syarat.Hasil. Empatpuluh subjek penelitian, didapatkan prevalensi inhibitor 37,5% (15/40). Rentang usia subjek 10 (1,5-18) tahun, usia saat diagnosis hemofilia pertama kali ditegakkan 8 bulan, dan saat pertama kali mendapat terapi faktor VIII pada inhibitor positif 9 bulan. Hampir seluruh subjek (39/40) mendapat terapi konsentrat plasma, 11/15 subjek dengan inhibitor positif mendapat terapi pertama kali sebelum berusia 1 tahun, 14/15 subjek merupakan hemofilia berat, sebagian besar (12/15) mendapat manifestasi perdarahan sendi. Suku bangsa ibu, Jawa, lebih sering ditemukan pada inhibitor positif (8/15). Tidak ditemukan hasil yang bermakna secara statistik antara faktor risiko dengan timbulnya inhibitor.Kesimpulan. Prevalensi inhibitor 37,5%, inhibitor positif lebih sering ditemukan pada pasien hemofilia berat yang mendapat terapi pertama kali sebelum berusia 1 tahun. Penelitian kami tidak berhasil membuktikan faktor risiko bermakna untuk timbulnya inhibitor pada anak dengan hemofilia A.

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Factor VIII gene mutations profile in 148 Chinese hemophilia A subjects

Cited by 25 publications

References 26 publications

Mutation spectrum and inhibitor risk in 100 Korean patients with severe haemophilia A

Mutation spectrum and inhibitor risk in 100 Korean patients with severe haemophilia A

Factor VIII genetic mutations and protein alterations in hemophilia A: A review

Faktor Risiko Timbulnya Inhibitor Faktor VIII pada Anak dengan Hemofilia A

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