Department of Laboratory Medicine, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, China.
Ann Hematol. 2024 Feb;103(2):645-652. doi: 10.1007/s00277-023-05487-w. Epub 2023 Nov 10.
Currently, limited information is available in the literature regarding the relationships between PROC mutations and clinical features in Chinese individuals. We aimed to characterize severe congenital Protein C deficiency in 22 unrelated Chinese families in a tertiary hospital by analyzing its clinical manifestation, associated risk factors, and gene mutations. We measured protein C activity and antigen levels for all participants, screened them for mutations in the PROC gene, and analyzed the clinical features of each family to identify commonalities and differences. The analysis revealed a total of 75 individuals with PCD and 16 different PROC mutations, including 12 missense mutations and 4 deletion mutations. Among them, 11 who were compound heterozygotes or homozygotes for mutations tended to develop symptoms at a younger age without any clear triggers. In contrast, the remaining 64 individuals who were heterozygotes for mutations often had clear triggers for their symptoms and experienced a milder course of the disease. It is worth noting that the mutation c.565C > T occurred most frequently, being identified in 8 out of 22 families (36%). Our team also reported five novel mutations, including c.742-744delAAG, c.383G > A, c.997G > A, c.1318C > T, and c.833T > C mutations. The identification of five novel mutations adds to the richness of the Human Genome Database. Asymptomatic heterozygotes are not uncommon, and they are prone to develop symptoms with obvious triggers. The evidence presented strongly suggest that asymptomatic individuals with family history of protein C deficiency can benefit from mutational analysis of PROC gene.
目前,关于 PROC 基因突变与中国人群临床特征的关系,文献报道有限。本研究旨在通过分析 22 个无血缘关系的中国家庭严重先天性蛋白 C 缺乏症的临床表现、相关危险因素和基因突变,对其进行研究。我们测量了所有参与者的蛋白 C 活性和抗原水平,对 PROC 基因突变进行了筛查,并对每个家庭的临床特征进行了分析,以确定其共性和差异。分析共发现 75 例 PCD 患者和 16 种不同的 PROC 基因突变,包括 12 种错义突变和 4 种缺失突变。其中 11 例复合杂合子或纯合子突变患者发病年龄较早,无明显诱因。相比之下,其余 64 例突变杂合子患者的症状常受明确诱因影响,疾病过程较轻。值得注意的是,c.565C>T 突变最为常见,22 个家系中有 8 个(36%)携带该突变。我们的团队还报道了 5 种新的突变,包括 c.742-744delAAG、c.383G>A、c.997G>A、c.1318C>T 和 c.833T>C 突变。这 5 种新突变的发现丰富了人类基因组数据库。无症状杂合子并不少见,且容易出现有明确诱因的症状。这些证据表明,有蛋白 C 缺乏症家族史的无症状个体可以从 PROC 基因突变分析中获益。