Identification of two novel mutations in non‐Jewish factor XI deficiency
Identification of two novel mutations in non‐Jewish factor XI deficiency
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鉴定非犹太因子 XI 缺乏症的两种新突变
DOI：
10.1111/j.1365-2141.1995.tb05215.x
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发表时间：
1995
影响因子：
6.5
通讯作者：
J. McVey
中科院分区：
文献类型：
--
作者：
Y. Imanaka;K. Lal;T. Nishimura;P. Bolton;EDWARD G. D. Titddenham;J. McVey
摘要我们研究了2例杂合子无关CRM非犹太FXI缺陷患者。这两名患者都没有携带先前描述的突变。通过PCR扩增每个外显子和侧翼内含子序列后的SSCP分析筛选它们的FXI基因。对显示异常迁移率的DNA片段进行克隆和测序。发现了以下突变：在病例1中，外显子12中的T至G转换导致Phe-442被瓦尔取代（FXI-F442 V）;在病例2中，外显子5中的C至A转换导致Cys-128被无义密码子取代（FXI-C128 X）。错义突变导致FXI的蛋白酶结构域内的取代。分子建模将该残基定位在蛋白酶结构域的结构保守区域中，因此氨基酸取代可能干扰链折叠和随后的分泌或血浆中蛋白质的稳定性。我们的结论是，我们已经确定的突变是负责这些患者的遗传异常。
Summary. We have studied two heterozygous unrelated CRM non‐Jewish FXI‐deficient patients. Neither of the patients carries a previously described mutation. Their FXI genes were screened by SSCP analysis following PCR amplification of each exon and the flanking intronic sequences. DNA fragments showing aberrant mobility were cloned and sequenced. The following mutations were identified: in case 1, a T to G transition in exon 12 results in the substitution of Phe‐442 by Val (FXI‐F442V); in case 2 a C to A transition in exon 5 results in the substitution of Cys‐128 by a nonsense codon (FXI‐C128X). The missense mutation results in a substitution within the protease domain of FXI. Molecular modelling locates this residue in a structurally conserved region of the protease domain and the amino acid substitution may therefore interfere with either chain folding and subsequent secretion or the stability of the protein in plasma. We conclude that the mutations which we have identified are responsible for the inherited abnormality in these patients.
影响因子：
20.3
作者：
D. Gailani;G. Broze
通讯作者：
D. Gailani;G. Broze
影响因子：
2.9
作者：
DAVIE, EW;FUJIKAWA, K;KISIEL, W
通讯作者：
KISIEL, W
德系犹太人的 XI 因子（血浆凝血活酶前体）缺乏症是一种出血性疾病，可能由三种类型的点突变引起。
DOI：
10.1073/pnas.86.20.7667
发表时间：
1989
影响因子：
11.1
作者：
Asakai,R;Chung,DW;Ratnoff,OD;Davie,EW
通讯作者：
Davie,EW