一个遗传性蛋白C缺陷症家系表型与基因突变分析

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Abstract Objective: To ascertain the mutant gene of a family with hereditary protein C (PC) deficiency and to explore the molecular pathogenesis. Methods: The plasma protein C activity (PC:A), protein C antigen (PC:Ag) and other coagulation index of the family members were measured. For the proband, potential mutations in exons, flanking introns and 5’, 3’untranslated regions of PROC gene were screened by direct DNA sequencing. The Mutational site was further detected in the other family members. The ClustalX-2.1-win software and the online bioinformatics tool PolyPhen-2 were used to checke the conservatism and the possible impact of the mutation respectively. Structural analysis of the mutational site was processed with software Swiss-PdbViewer and PIC program. Results: The proband, her son and sister had reduced level of PC:A and PC:Ag among 39%~58%. Gene sequencing revealed that three people carried a heterozygous mutation c.997G>A in exon 9 of PROC gene resulting in a substitution of Alanine 291 by Threonine (p.Ala291Thr). According to the results of bioinformatics software analysis, p.Ala291Thr was “probably damaging” and Ala291 was not highly conserved. Model analyzing illuminated that replacement of Ala291 with Thr291 led to additional hydrogen bonding between Thr291-Pro327, affecting the normal spatial conformation and stability of protein. Conclusion: The proband carried a heterozygous mutation c.997G>A in exon 9 resulting in p.Ala291Thr which is a novel mutation. The p.Ala291Thr mutation could potentially account for the reduced activity of PC in this pedigree.

Key words： protein c deficiency inherited gene mutation model analysis

Received: 02 December 2018

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	LIU Meina
	SU Kankan
	ZHANG Haiyue
	JIN Yanhui
	YANG Lihong
	LI Xiaolong
	WANG Mingshan

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https://xb.wmu.edu.cn/EN/ OR https://xb.wmu.edu.cn/EN/Y2019/V49/I4/277

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