Analysis of genetic variant in a Chinese pedigree with hereditary factor XIII deficiency
10.3760/cma.j.cn511374-20210527-00448
- VernacularTitle:一例遗传性凝血因子F13缺陷症家系的基因变异分析
- Author:
Haixiao XIE
1
;
Lihong YANG
;
Huinan XIA
;
Yanhui JIN
;
Xiaolong LI
;
Shuting JIANG
;
Yaoyao XU
;
Mingshan WANG
Author Information
1. 温州医科大学附属第一医院医学检验中心，浙江 325015
- Keywords:
Factor XIII deficiency;
Variant;
Rare bleeding disorder;
Model analysis
- From:
Chinese Journal of Medical Genetics
2022;39(7):708-712
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the genetic basis for a patient with factor XIII (FXIII) deficiency.Methods:All exons of the F13A1 and F13B genes were amplified by PCR and sequenced directly. The sequencing was performed with a reverse primer if a variant was found. Conservation of variant site was analyzed by the ClustalX software. Four online bioinformatic software including MutationTaster, PolyPhen-2, PROVEAN and SIFT were used to predict the function of the mutation site. The Swiss-PdbViewer software was applied to analyze the changes in the protein model and intermolecular force. Results:The proband was found to harbor a novel c. 515G>C (p.Arg171Pro) variant of the F13A1 gene. The corresponding amino acid Arg171 is conserved among homologous species. Bioinformatic analysis indicated that Arg171Pro variant may affect the protein function. Protein model analysis showed that in the wild-type, there is one hydrogen bond between Arg171 and Pro27; one hydrogen bond between Arg171 and Thr28; two hydrogen bonds between Arg171 and Glu102. When Arg171 was mutated to Pro171, the three hydrogen bonds between Arg171 and Pro27, Glu102 are all disappeared and formed a new benzene ring which might affect the stability of the protein structure. No variant was found in the F13B gene. Conclusion:The Arg171Pro variant may account for the decreased FXIII level. Above finding has enriched the spectrum of F13A1 gene variants.
