Liang Wei-Ling, Wei Hong-Ying, Liao Ning, Zhou Jun-Li
Department of Pediatrics, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2015 Sep;17(9):903-7.
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.
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.
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.
FVIII gene exon 14 is a hot-spot mutation region and p.His1202LeufsX16 is found to be a novel mutation in FVIII gene.
研究7个甲型血友病（HA）家系患者的凝血因子VIII（FVIII）基因突变类型以及FVIII基因突变与临床表型之间的关系。
招募了来自7个HA家系的8例患者。检测这些患者的活化部分凝血活酶时间（APTT）和凝血因子VIII促凝活性（VIII:C）。采用聚合酶链反应（PCR）分析FVIII基因内含子1和22的倒位情况。对于无FVIII内含子倒位的患者，进行直接测序以确定其突变类型，并对其家系中的其他相关成员也进行PCR和测序检测，以分析相应的突变位点。
8例患者的APTT范围为91.6 - 131秒，VIII:C范围为0.8% - 2%。未检测到FVIII基因内含子22倒位，仅在1例患者中检测到内含子1倒位。其余7例患者共检测到FVIII基因5种突变类型，其中6例患者外显子14发生突变，1例患者外显子23发生突变；所有5种突变类型均为单核苷酸突变。在检测到的FVIII基因突变中，1例患者检测到的p.His1202LeufsX16（c.3666delA）为FVIII基因中此前未报道的突变。
FVIII基因外显子14是热点突变区域，且p.His1202LeufsX16是FVIII基因中的新突变。
