2个F13A1变异的复合杂合性导致因子XIII缺失

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis Pub Date : 2025-07-01 DOI:10.1016/j.rpth.2025.102978

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

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引用次数: 0

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，辅助生化分析，可以提供有价值的诊断和临床清晰度。我们描述了一个病例的儿童与FXIII缺乏症，其中基因组研究是准确诊断和治疗的关键。临床方法一名8岁男性，表现为严重出血表型。患者FXIII抗原、活性和α -亚单位（FXIIIA）水平均低于检测限。遗传分析确定了F13A1的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）。三人组分析显示，p.Ser20X和p.Arg704Gln变异的复合杂合性是导致指标病例中严重的FXIIIA缺陷的原因。结论家族分离研究对于解释遗传分析结果和确定导致严重FXIIIA缺乏的致病变异至关重要。

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Factor XIII deficiency due to compound heterozygosity for 2 F13A1 variants

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 F13A1: 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.

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