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
- 1Department of Laboratory Medicine, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, Wenzhou, China
- 2Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang China
Abstract
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.
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BibTeX
@article{wang2026genetic,
title = {{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}},
author = {Fengjiao Wang and Haixiao Xie and Xingxing Zhou and Ling You and Mingshan Wang and Lihong Yang},
journal = {Annals of Hematology},
year = {2026},
month = jul,
doi = {10.1007/s00277-026-07204-9},
url = {https://doi.org/10.1007/s00277-026-07204-9},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Fengjiao Wang
AU - Haixiao Xie
AU - Xingxing Zhou
AU - Ling You
AU - Mingshan Wang
AU - Lihong Yang
PY - 2026
DA - 2026/07/29
JO - Annals of Hematology
DO - 10.1007/s00277-026-07204-9
UR - https://doi.org/10.1007/s00277-026-07204-9
AB - 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.
SN - 0939-5555
SN - 1432-0584
ER -