KNG1基因突变致高分子量激肽原缺乏症的实验室诊断逻辑分析及文献复习OA

Objective High molecular weight kininogen(HMWK)deficiency is an extremely rare autosomal recessive coagulation disorder.Patients are often identified incidentally due to marked-ly prolonged activated partial thromboplastin time(APTT)on screening.This study reported a rare case caused by a homozygous variant in exon 5 of the KNG1 gene and comparatively analyzed its labo-ratory characteristics with those of other coagulation disorders.Methods The clinical data of a pa-tient with homozygous KNG1 c.628_629del variant(HMWK proband)were analyzed.Patients with inhibitor-positive hemophilia A(HA),inhibitor-negative hemophilia B(HB),and lupus anticoagu-lant(LA)positivity in the same period were enrolled as controls.Coagulation parameters,coagulation factor activities,coagulation factor inhibitors,APTT mixing studies,and thromboelastography(TEG)parameters were compared among groups.Results The HMWK proband presented with markedly prolonged APTT(＞120 s),but without reduced coagulation factor activities,and no FV Ⅲ:C or FIX:C inhibitors were detected.The APTT was fully corrected immediately and after 2-hour incubation upon mixing with control plasma,demonstrating a typical correction pattern consistent with factor de-ficiency.TEG revealed highly abnormal R time,K time,α angle,and maximum amplitude(MA),all of which supported the diagnosis of contact activation factor deficiency.Genetic testing ultimately confirmed a homozygous deletion variant in exon 5 of the KNG1 gene.Conclusion The KNG1 c.628_629del variant leads to HMWK deficiency.A combination of routine coagulation tests,coag-ulation factor assays,inhibitor screening,APTT mixing studies,and TEG can effectively identify this rare disorder.