Genetic and clinical phenotype analysis of a case of high-molecular-weight kininogen deficiency caused by a frameshift mutation c.628_629delAA in the KNG1 gene

Hereditary high molecular weight kininogen (HMWK) deficiency is a rare autosomal recessive disorder characterized by a markedly prolonged activated partial thromboplastin time (APTT) without an associated bleeding diathesis. We report a patient presenting with significant APTT prolongation and profoundly reduced HMWK activity. Genetic analysis identified a novel homozygous deletion, c.628_629delAA, in exon 5 of the KNG1 gene, resulting in a p.Asn210Phe fs*15 frameshift mutation. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, this mutation was classified as pathogenic. This mutation introduces a premature termination codon (PTC), leading to protein truncation. Family members carrying the heterozygous mutation exhibited mildly decreased HMWK activity but maintained normal APTT values. This case not only expands the mutational spectrum of the KNG1 gene but also deepens the understanding of the genetic characteristics of HMWK deficiency but also underscores the clinical importance of performing systematic genetic screening in both patients and their family members.