[Analysis of two consanguineous Chinese pedigrees affected with Hereditary prokallikrein deficiency and High molecular weight kininogen deficiency]

doi:10.3760/cma.j.cn511374-20230901-00105

科研成果详情

题名	[Analysis of two consanguineous Chinese pedigrees affected with Hereditary prokallikrein deficiency and High molecular weight kininogen deficiency]
其他题名	Analysis of two consanguineous Chinese pedigrees affected with Hereditary prokallikrein deficiency and High molecular weight kininogen deficiency
作者	Bile Chen; Zuoting Xie; Zhou Zheng; Yuan Chen; Huilin Chen; Mingshan Wang; Yanhui Jin
发表日期	2024-09-10
发表期刊	Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 影响因子和分区
语种	中文
原始文献类型	English Abstract ; Journal Article
关键词	激肽释放酶原缺陷症高分子量激肽原缺陷症 KLKB1基因 KNG1基因
其他关键词	Prokallikrein deficiency ; High molecular weight kininogen deficiency ; KNG1 gene ; KLKB1 gene
摘要	To analyze the laboratory phenotype and genetic variants of two consanguineous Chinese pedigrees affected with Hereditary prokallikrein (PK) and High molecular weight kininogen (HMWK) deficiency and explore their molecular pathogenesis., A PK deficiency pedigree (10 individuals from 4 generations) and a HMWK deficiency pedigree (6 individuals from 3 generations) which were admitted to the First Affiliated Hospital of Wenzhou Medical University on December 3, 2021 and June 16, 2022, respectively were selected as the study subjects. Clinical data of the two pedigrees were collected, and the related coagulation indexes of the probands and their family members were determined. Genomic DNA of the two pedigrees was extracted from peripheral blood samples. All of the exons and flanking sequences of the KLKB1 and KNG1 genes of the probands were analyzed by direct sequencing. And the corresponding sites were sequenced among other family members. Bioinformatic software was used to analyze the conservation of variation sites and the effect of variant on the protein function., The plasma PK activity of proband 1, a 29-year-old female, and her brother were extremely low (< 1.0%). Proband 2 was a 66-year-old male with extremely low plasma HMWK activity (< 1.0%). Genetic sequencing revealed that the proband 1 and her brother had both harbored a homozygous c.417_418insCATTCTTA (p.Arg140Hisfs3) insertional variant in exon 5 of the KLKB1 gene. Proband 2 had harbored a homozygous c.460C>A (p.Pro154Thr) missense variant in exon 4 of the KNG1 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were respectively rated as pathogenic (PVS1+PM2_Supporting+PM4) and likely pathogenic (PS4+PM2_Supporting+PP3+PP4)., The c.417_418insCATTCTTA (p.Arg140Hisfs3) variant of the KLKB1 gene and the c.460C>A (p.Pro154Thr) variant of the KNG1 gene probably underlay the decreased PK and HMWK activities in the two pedigrees, respectively.
其他摘要	Objective:To analyze the genetic variants of two consanguineous Chinese pedigrees affected with Hereditary prokallikrein (PK) and High molecular weight kininogen (HMWK) deficiency and explore their molecular pathogenesis.Methods:A PK deficiency pedigree (10 individuals from 4 generations) and a HMWK deficiency pedigree (6 individuals from 3 generations) which were admitted to the First Affiliated Hospital of Wenzhou Medical University on December 3, 2021 and June 16, 2022, respectively were selected as the study subjects. Clinical data of the two pedigrees were collected, and the related coagulation indexes of the probands and their family members were determined. Genomic DNA of the two pedigrees was extracted from peripheral blood samples. This study was approved by the First Affiliated Hospital of Wenzhou Medical University (Ethics No. KY2022-R193).Results:The plasma PK activity of proband A, a 29-year-old female, and her brother were extremely low (< 1.0%). Proband B was a 66-year-old male with extremely low plasma HMWK activity (< 1.0%). Genetic sequencing revealed that the proband A and her brother had both harbored a homozygous c. 417_418insCATTCTTA (p.Arg140Hisfs3) insertional variant in exon 5 of the KLKB1 gene, with her grandmother, maternal grandmother, father, mother, sister and son all carrying heterozygous insertion variant, and her ancestor father and husband are both wild-type. Proband B had harbored a homozygous c. 460CA (p.Pro154Thr) missense variant in exon 4 of the KNG1 gene, and his son carries a heterozygous missense variant. All other members of the pedigree are wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were respectively rated as pathogenic (PVS1+ PM2_Supporting+ PM4) and likely pathogenic (PS4+ PM2_Supporting+ PP3+ PP4). Conclusion:The c. 417_418insCATTCTTA (p.Arg140Hisfs3) variant of the KLKB1 gene and the c. 460CA (p.Pro154Thr) variant of the KNG1 gene probably underlay the decreased PK and HMWK activities in the two pedigrees, respectively.
ISSN	1003-9406
卷号	41 期号:9 页码:1066-1071
DOI	10.3760/cma.j.cn511374-20230901-00105
页数	6
收录类别	PUBMED ; SCOPUS ; 万方 ; CSCD ; ISTIC ; 北大核心
URL	查看原文
PubMed ID	39217484
SCOPUSEID	2-s2.0-85203110825
Scopus学科分类	Medicine (all)
SCOPUS_ID	SCOPUS_ID:85203110825
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/217710
专题	附属第一医院第一临床医学院（信息与工程学院）、附属第一医院附属第一医院_输血科
作者单位	Department of Blood Transfusion, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, China. jyh603@126.com.
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院; 输血科
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Bile Chen,Zuoting Xie,Zhou Zheng,et al. [Analysis of two consanguineous Chinese pedigrees affected with Hereditary prokallikrein deficiency and High molecular weight kininogen deficiency][J]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics,2024,41(9):1066-1071.
APA	Bile Chen., Zuoting Xie., Zhou Zheng., Yuan Chen., Huilin Chen., ... & Yanhui Jin. (2024). [Analysis of two consanguineous Chinese pedigrees affected with Hereditary prokallikrein deficiency and High molecular weight kininogen deficiency]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics, 41(9), 1066-1071.
MLA	Bile Chen,et al."[Analysis of two consanguineous Chinese pedigrees affected with Hereditary prokallikrein deficiency and High molecular weight kininogen deficiency]".Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 41.9(2024):1066-1071.