Analysis of novel gene mutations in a family with hereditary coagulation factor XI deficiency
10.3760/cma.j.cn114452-20240123-00043
- VernacularTitle:分析1个遗传性凝血因子Ⅺ缺陷症家系的基因新突变
- Author:
Rui LI
1
;
Yarong XIE
;
Wei ZHU
;
Xiaoyan LI
;
Hao LIU
Author Information
1. 运城市中心医院检验科，运城 044000
- Keywords:
Factor Ⅺ Deficiency;
Inherited coagulation factor Ⅺ deficiency;
Novel mutations;
Bioinformatics
- From:
Chinese Journal of Laboratory Medicine
2024;47(8):952-957
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the molecular mechanism of clinical bleeding in a family with hereditary coagulation factor Ⅺ (FⅪ) deficiency caused by a novel mutation of the coagulation factor Ⅺ (FⅪ) gene.Methods:A male proband with hereditary coagulation factor XI deficiency who was admitted to Yuncheng Central Hospital Affiliated to Shanxi Medical University due to "adenoid hypertrophy" on February 23, 2023 and his family members (5 people in 3 generations) were selected as research subjects. The clinical data of the proband and family members were collected; the relevant coagulation indexes of all members were tested; those with abnormal coagulation indexes (prolonged activated partial thromboplastin time (APTT), normal thrombin time (PT) and fibrinogen (Fib)) were selected for APTT correction experiment; those with corrected Rosner index (RI) less than 10% were selected to detect FⅪ activity (FⅪ:C) by one-step method, FⅪ antigen (FⅪ:Ag) by ELISA method, and whole exon sequence by Illumina sequencing method. New mutation sites were rated according to the American College of Medical Genetics and Genomics (ACMG) related variation rating guidelines, and bioinformatics software was used to predict the impact of new mutations on protein structure and function.Results:The APTT of the proband, his father and his daughter were all prolonged and their RI were all less than 10%. Further tests revealed that FⅪ:C and FⅪ:Ag of the three were all decreased. Illumina sequencing revealed a new frameshift mutation c.1223dupC (P.Ser409Leufs*32) in exon 11 of FⅪ of the three people, and a missense mutation c.G1253T (p.Gly418Val) in exon 11 of FⅪ of the proband′s father. ACMG rated the new mutation as pathogenic, and c.G1253T was a reported possible pathogenic mutation.Conclusion:The heterozygous frameshift mutation c.1223dupC (P.Ser409Leufs*32) in exon 11 of FⅪ may be the main molecular mechanism of the disease in this family.
