Relationship between genotypes and clinical phenotypes in patients from 7 hemophilia A families

LIANG Wei-Ling; WEI Hong-Ying; LIAO Ning; ZHOU Jun-Li

doi:10.7499/j.issn.1008-8830.2015.09.003

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Chinese Journal of Contemporary Pediatrics ›› 2015, Vol. 17 ›› Issue (9) : 903-907. DOI: 10.7499/j.issn.1008-8830.2015.09.003

CLINICAL RESEARCH

Relationship between genotypes and clinical phenotypes in patients from 7 hemophilia A families

LIANG Wei-Ling¹, WEI Hong-Ying¹, LIAO Ning¹, ZHOU Jun-Li²

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Abstract

Objective To study the mutation types of factor VIII (FVIII) gene in patients from 7 hemophilia A (HA) families and the relationship between FVIII gene mutations and clinical phenotypes.Methods A total of 8 patients from 7 HA families were recruited. The activated partial thromboplastin time (APTT) and factor VIII coagulant activity (VIII:C) in these patients were measured. Polymerase chain reaction (PCR) was performed to analyze FVIII gene intron 1 and 22 inversions. For patients without the FVIII intron inversions, direct sequencing was performed to determine their mutation types and other related members of their families were also tested by PCR and sequencing to analyze the corresponding mutation sites.Results The ranges of APTT and VIII:C of the 8 patients were 91.6-131 seconds and 0.8%-2%, respectively. FVIII gene intron 22 inversion was not detected, while intron 1 inversion was detected in one patient. There were 5 types of mutations in FVIII gene detected in the remaining 7 patients, including 6 patients with mutations in exon 14 and 1 patient with mutation in exon 23; all of the 5 types of mutations were single nucleotide mutations. Among the detected mutations in FVIII gene, p.His1202LeufsX16 (c.3666delA) detected in one patient was found to be a previously unreported mutation in FVIII gene.Conclusions FVIII gene exon 14 is a hot-spot mutation region and p.His1202LeufsX16 is found to be a novel mutation in FVIII gene.

Key words

Hemophilia A / Genotype / Clinical phenotype

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LIANG Wei-Ling, WEI Hong-Ying, LIAO Ning, ZHOU Jun-Li. Relationship between genotypes and clinical phenotypes in patients from 7 hemophilia A families[J]. Chinese Journal of Contemporary Pediatrics. 2015, 17(9): 903-907 https://doi.org/10.7499/j.issn.1008-8830.2015.09.003

References

[1] 中华医学会血液学会分会血栓与止血学组, 中国血友病协作组. 血友病诊断与治疗中国专家共识(2013 版) [J]. 中华血液学杂志, 2013, 34(5):461-463.
[2] Keeney S, Mitchell M, Goodeve A. The molecular analysis of haemophilia A:a guideline from the UK haemophilia centre doctors, organization haemophilia genetics laboratory network[J]. Haemophilia, 2005, 11(4):387-397.
[3] 梁燕, 赵耘, 王战勇, 等. 血友病甲基因分析技术的改进及其在产前诊断中的应用[J]. 中华医学遗传学杂志, 2007, 24(4):437-439.
[4] 周竣荔, 韦红英, 吴华, 等. STR 遗传标记在广西地区血友病 A 携带者诊断中的运用[J]. 中国当代儿科杂志, 2012, 14(14):951-955.
[5] 张之南, 杨天楹, 郝玉书. 血液病学[M]. 北京:人民卫生出版社, 2003:1724-1725.
[6] Liu Q, Nozari G, Sommer SS. Single-tube polymerase chain reaction for rapid diagnosis of the inversion hotspot of mutation in hemophilia A[J]. Blood, 1998, 92(4):1458-1459.
[7] 李坦, 戴菁, 吴竞生, 等. 血友病A 患者凝血因子Ⅷ基因内含子1 及22 倒位分析[J]. 中华血液学杂志, 2009, 30(3):150-153.
[8] Viel KR, Machiah DK, Warren DM, et al. A sequence variation scan of the coagulation factor VIII (FVIII) structural gene and associations with plasma FVIII activity levels[J]. Blood, 2007, 109(9):3713-3724.
[9] Lin SY, Su YN, Hung CC, et al. Mutation spectrum of 122 hemophilia A families from Taiwanese population by LD-PCR, DHPLC, multiplex PCR and evaluating the clinical application of HRM[J]. BMC Med Genet, 2008, 9:53.
[10] Bagnall RD, Waseem N, Green PM, et al. Recurrent inversion breaking intron l of the factor VIII gene is a frequent cause of severe hemophilia A[J]. Blood, 2002, 99(1):168-174.
[11] Nadja B, Ameni M, Reswith E, et al. Spectmm of molecular defects and mutation deteetion rate in patients with mild and moderate hemophilia A[J]. Hum Mutat, 2007, 28(1):54-60.
[12] Zimmermann MA, Oldenburg J, Müller CR, et al. Unusual genomic rearrangements in introns 1 and 22 of the F8 gene[J]. Hamostaseologie, 2011, 31 Suppl 1:S69-S73.
[13] Bogdanova N, Markoff A, Pollmann H, et al. Prevalence of small rearrangements in the factor VIII gene F8C among patients with severe hemophilia A[J]. Hum Mutat, 2002, 20(3):236-237.
[14] Pelak K, Shianna KV, Ge D, et al. The characterization of twenty sequenced human genomes[J]. PLoS Genet, 2010, 6(9):e1001111.
[15] Santacroce R, Acquila M, Belvini D, et al. Identification of 217 unreported mutations in the F8 gene in a group of 1,410 unselected Italian patients with hemophilia A[J]. J Hum Genet, 2008, 53(3):275-284.
[16] 李汶, 胡晓, 高伯笛, 等. 10 个甲型血友病家系F Ⅷ基因突变分析[J]. 中华遗传学杂志, 2011, 28(2):127-132.
[17] Bowen DJ. Haemophilia A and haemophilia B:molecular insights[J]. Mol Pathol, 2002, 55(1):1-18.