Ma Rui-Xue, Li Hai-Yan, Zhang Yi-Hang, Zhang Xue-Min, Chen Yan-Juan, Dai Yi-Lin, Li Gui-Xian, Luo Wen-Hai, Zhang Jie, Tian Yun-Fen
College of Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China.
Department of Pediatrics, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
Front Pediatr. 2025 Jul 2;13:1555426. doi: 10.3389/fped.2025.1555426. eCollection 2025.
Factor XII (FXII) deficiency (OMIM 234000) is a rare hereditary coagulation disorder caused by pathogenic variants within the gene. It causes prolonged activated partial thromboplastin time without bleeding diathesis. Most patients have no obvious clinical symptoms, so the disease is difficult to be detected.
Here, we reported two pediatric cases with FXII deficiency from Kunming, China. Patient 1 was a 10-year-old girl who was hospitalized with a fever and cough for one week and diagnosed with pneumonia. Auxiliary coagulation function examination suggested that the activated partial thrombin time (APTT) was significantly prolonged, while both the coagulation factor XII activity (FXII:C) and coagulation factor XII antigen (FXII:Ag) were decreased. Whole exome sequencing (WES) revealed this patient carries compound heterozygous variants with NM_000505.4:c.509G>A (p.Cys170Tyr) and NM_000505.4:c.800+1G>C. Patient 2 was a newborn boy with prolonged coagulation of the umbilical cord and difficult hemostasis after birth. A prolonged APTT and a decreased ratio of FXII:C were observed. WES revealed this patient carries compound heterozygous variants with NM_000505.4:c.583del (p.His195Thrfs*56) and NM_000505.4:c.805C>T (p.Pro269Ser). RT-PCR assays demonstrated c.800+1G>C intron mutation resulted to a 166-bp deletion (exon 8 skipping) for patient 1. Bioinformatics analysis confirmed the pathogenicity of all four variants.
We presented two pediatric cases with FXII deficiency caused by novel compound heterozygous variants. Pediatricians should raise awareness of this rare and underdiagnosed disorder and improve diagnostic and intervention strategies.
凝血因子 XII（FXII）缺乏症（OMIM 234000）是一种由该基因内的致病变异引起的罕见遗传性凝血障碍。它导致活化部分凝血活酶时间延长，但无出血倾向。大多数患者没有明显的临床症状，因此该病难以被发现。
在此，我们报告了两例来自中国昆明的小儿 FXII 缺乏症病例。病例 1 是一名 10 岁女孩，因发热咳嗽住院一周，被诊断为肺炎。辅助凝血功能检查提示活化部分凝血酶时间（APTT）显著延长，而凝血因子 XII 活性（FXII:C）和凝血因子 XII 抗原（FXII:Ag）均降低。全外显子测序（WES）显示该患者携带 NM_000505.4:c.509G>A（p.Cys170Tyr）和 NM_000505.4:c.800+1G>C 的复合杂合变异。病例 2 是一名新生儿男孩，出生后脐带凝血时间延长且止血困难。观察到 APTT 延长和 FXII:C 比值降低。WES 显示该患者携带 NM_000505.4:c.583del（p.His195Thrfs*56）和 NM_000505.4:c.805C>T（p.Pro269Ser）的复合杂合变异。RT-PCR 检测表明，病例 1 的 c.800+1G>C 内含子突变导致 166 碱基对缺失（外显子 8 跳跃）。生物信息学分析证实了所有四个变异的致病性。
我们报告了两例由新型复合杂合变异引起的小儿 FXII 缺乏症病例。儿科医生应提高对这种罕见且诊断不足的疾病的认识，并改进诊断和干预策略。
