Severe high-molecular-weight kininogen deficiency due to a homozygous c.1456C > T nonsense variant in a large Chinese family.

Abstract

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*).

• Authors: Jing Yang, Liankai Fan, Yacui Qiao, Yongqiang Zhao, Tienan Zhu
• Journal: Journal of thrombosis and thrombolysis (J Thromb Thrombolysis) Vol. 50 Issue 4 Pg. 989-994 (Nov 2020) ISSN: 1573-742X [Electronic] Netherlands
• PMID: 32185598 (Publication Type: Case Reports, Journal Article)

Chemical References

• Codon, Nonsense
• Kininogen, High-Molecular-Weight
• Prekallikrein

Topics

• Aged
• Asian People
• Asymptomatic Diseases
• Blood Coagulation Disorders (blood, diagnosis, genetics)
• Blood Coagulation Tests (methods)
• Codon, Nonsense
• Family
• Female
• Homozygote
• Humans
• Kininogen, High-Molecular-Weight (blood, deficiency, genetics)
• Male
• Medical History Taking
• Middle Aged
• Partial Thromboplastin Time (methods)
• Pedigree
• Prekallikrein (metabolism)