severe high-molecular-weight kininogen deficiency due to a homozygous c.1456c > t nonsense variant in a large chinese family

High-molecular-weight kininogen (hmwk) deficiency is a very rare hereditary disorder caused by a defect of kininogen-1 gene (kgn1). a 67-year-old asymptomatic male with an isolated prolonged activated partial thromboplastin time (aptt) was recognized to have hmwk deficiency. the propositus had less than 1% hmwk procoagulant activity. the plasma hmwk procoagulant activities of his 2 younger sisters were 1.1% and less than 1%, respectively. prekallikrein (pk) activity was also reduced in the propositus and two of his younger sisters with severe hmwk deficiency. genetic testing to identify the kgn1 mutation provides a precise diagnosis for the patient and other family members. this chinese family has a novel kgn1 nonsense variant, c to t, at nucleotide position 1456 leading to a stop codon in position 486 (p. gln486*).