因两个变异体的复合杂合性导致的因子 XIII 缺乏症。

Factor XIII deficiency due to compound heterozygosity for 2 variants.

作者信息

Odame Jodie, Malcolmson Caroline, Wakefield Cindy, Bourque Tammy, Lillicrap David, Rawley Orla, Bowman Mackenzie, Carcao Manuel, Bouskill Vanessa

机构信息

Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Faculty of Medicine, Toronto, Canada.

Department of Nursing, The Hospital for Sick Children, Toronto, Canada.

出版信息

Res Pract Thromb Haemost. 2025 Jul 22;9(5):102978. doi: 10.1016/j.rpth.2025.102978. eCollection 2025 Jul.

DOI:10.1016/j.rpth.2025.102978

PMID:40893649

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12395524/

Abstract

BACKGROUND

Factor (F)XIII deficiency is a rare bleeding disorder. Genomic studies, adjunctive to biochemical assays, can provide valuable diagnostic and clinical clarity.

KEY CLINICAL QUESTION

We describe a case of a child with FXIII deficiency in which genomic studies were crucial for accurate diagnosis and treatment.

CLINICAL APPROACH

An 8-year-old male presented with a severe bleeding phenotype. His FXIII antigen, activity, and alpha-subunit (FXIIIA) levels were below detection limits. Genetic analysis identified 2 likely pathogenic variants in : a novel nonsense variant (c.59_60del, p.Ser20X) and a missense variant (c.211G>A, p.Arg704Gln). Trio analysis revealed that compound heterozygosity for the p.Ser20X and p.Arg704Gln variants were causal for severe FXIIIA deficiency in the index case.

CONCLUSION

Family segregation studies were essential in this case for interpreting genetic analysis results and identifying the causative variants resulting in severe FXIIIA deficiency.

摘要

背景

因子（F）XIII缺乏症是一种罕见的出血性疾病。基因组研究作为生化检测的辅助手段，可为诊断和临床提供有价值的清晰度。

关键临床问题

我们描述了一例FXIII缺乏症患儿，其中基因组研究对准确诊断和治疗至关重要。

临床方法

一名8岁男性表现出严重的出血表型。他的FXIII抗原、活性和α亚基（FXIIIA）水平低于检测限。基因分析在[具体基因名称未给出]中鉴定出2个可能的致病变异：一个新的无义变异（c.59_→60del，p.Ser20X）和一个错义变异（c.211G>A，p.Arg704Gln）。三联体分析显示，p.Ser20X和p.Arg704Gln变异的复合杂合性是导致索引病例严重FXIIIA缺乏的原因。