F5 유전자에서 새로운 변이를 포함한 복합 이형 접합 변이 1예 보고
Congenital Factor V Deficiency from Compound Heterozygous Mutations with a Novel Variant c.5403del (p.Lys1801AsnfsTer11) in the F5 Gene: A Case Report
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초록
선천성 제V인자 결핍증(FVD)은 낮은 혈청 제V인자 수치가 특징인질환으로 임상 증상이 무증상부터 치명적인 출혈까지 다양하기 때문에 정확한 진단이 중요하다. 저자들은 새로운 변이를 포함하는FVD 환자 1예를 보고한다. 낮은 제V인자 활성도를 보이는 50세 남성에 대한 유전자 검사가 의뢰되었다. c.286G>C (p.Asp96His) 변이와 새로운 변이인 c.5403del (p.Lys1801AsnfsTer11)가 확인되었다. 문헌에 따르면 c.286G>C (p.Asp96His) 변이는 F5 유전자의 A1 도메인에 위치하며 단백질 접힘에 영향을 주어 세포 내 이동과 분비를 방해한다. 새로운 변이인 c.5403del (p.Lys1801AsnfsTer11)은 C1 도메인에 위치하며 프레임 이동을 유발하여 조기 절단을 유발할것으로 예측된다. 제V인자 활성도가 FVD 중증도와 반드시 일치하는 것은 아니므로 정확한 진단을 통해 예상치 못한 출혈을 예방하기 위해서 임상적으로 FVD가 의심되는 경우 적극적인 유전자 검사가 필요하다.
Abstract
Congenital factor V (FV) deficiency (FVD) is characterized by low serum FV levels. Because its’ clinical symptoms vary from asymptomatic to lifethreatening bleeding, accurate diagnosis is critical. We report a case of a patient with FVD and compound heterozygous variants, including a novel pathogenic variant. A 50-year-old man with a low FV activity underwent genetic analysis. The c.286G>C (p.Asp96His) and the novel variant, c.5403del (p.Lys1801AsnfsTer11), were confirmed. The c.286G>C (p.Asp96His) variant is located in the A1 domain of the F5 gene, affecting folding and interfering with intracellular trafficking and secretion. On the other hand, the novel c.5403del (p.Lys1801AsnfsTer11) variant is located in the C1 domain and is predicted to cause a frameshift, resulting in premature truncation. FV activity does not always correlate with clinical severity in patients with FVD. Thus, achieving a precise diagnosis of FVD is crucial to prevent unexpected bleeding accidents. Therefore, active genetic tests should be performed when FVD is clinically suspected.
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