Zhang Huifei, Bi Xiaojie, Su Zhengxian, Tu Xi, Wang Lizhen, Shen Bo
Department of Clinic Laboratory, The Taizhou Hospital of Zhejiang Province.
Department of Clinic Laboratory, Taizhou Enze Hospital.
Blood Coagul Fibrinolysis. 2018 Mar;29(2):216-219. doi: 10.1097/MBC.0000000000000687.
: Neonatal purpura fulminans is a rare, life-threatening disease caused by severe congenital deficiency of protein C (PC) because of homozygous or compound heterozygous mutations in the PROC gene. Mutation analysis plays a critical role in diagnosing the disorder and offering prenatal guidance. In this study, we identified a genetic defect in the PROC gene leading to neonatal purpura fulminans. The propositus had very low PC activity (4%) and PC antigen activity (5%). DNA screening of the whole PROC gene revealed two compound heterozygous mutations in exon8 (c.795_796insA) and exon9 (c.1206_1207insG). These two variations led to the compound heterozygous mutations of Gly266Argfs4 and Pro405Alafs20, which were inherited from the patient's father and mother, respectively. His older sister is heterozygous for the Gly266Argfs4 mutation. The inserted nucleotides alter the protein by introducing a stop codon at the subsequent AA position, resulting in a truncated protein compared with the wild type. We deduced that the compound heterozygous mutations are responsible for the PC deficiency, the Gly266Argfs4 mutation has been confirmed to be a novel mutation.
新生儿暴发性紫癜是一种罕见的、危及生命的疾病，由PROC基因的纯合或复合杂合突变导致严重的先天性蛋白C（PC）缺乏引起。突变分析在诊断该疾病和提供产前指导方面起着关键作用。在本研究中，我们鉴定了PROC基因中的一个导致新生儿暴发性紫癜的遗传缺陷。先证者的PC活性极低（4%），PC抗原活性为（5%）。对整个PROC基因进行DNA筛查发现外显子8（c.795_796insA）和外显子9（c.1206_1207insG）存在两个复合杂合突变。这两个变异导致了Gly266Argfs4和Pro405Alafs20的复合杂合突变，分别遗传自患者的父亲和母亲。他的姐姐是Gly266Argfs4突变的杂合子。插入的核苷酸通过在随后的氨基酸位置引入终止密码子来改变蛋白质，导致与野生型相比产生截短的蛋白质。我们推断复合杂合突变是PC缺乏的原因，Gly266Argfs4突变已被证实是一种新突变。
