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SERPINF2 – Alpha-2-plasmin Inhibitor Deficiency

Heterozygous missense variants in SERPINF2 cause an autosomal dominant bleeding disorder characterized by reduced alpha-2-plasmin inhibitor activity and antigenic levels. A G→A substitution (c.1231G>A (p.Val411Met)) was identified in three related individuals presenting with traumatic haematoma, peri-/postoperative bleeding, transfusion requirement after delivery, and prolonged bleeding post-extraction; plasma inhibitor activities were reduced to 49–66% and antigen concentrations to 57–68% of normal (PMID:10583218). The variant segregated with disease and was absent in one unaffected family member and 30 blood donors. Functional assays confirmed haploinsufficiency of alpha-2-plasmin inhibitor consistent with the clinical phenotype. Although evidence is limited to a single family, these data support a causative role of SERPINF2 variants in alpha-2-plasmin inhibitor deficiency. Key take-home: SERPINF2 testing should be considered in autosomal dominant bleeding syndromes with decreased plasmin inhibitor levels.

References

  • British journal of haematology • 1999 • A novel missense mutation in the human plasmin inhibitor (alpha2-antiplasmin) gene associated with a bleeding tendency. PMID:10583218

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Heterozygous missense variant segregating in one family across three affected members ([PMID:10583218]); supportive biochemical evidence

Genetic Evidence

Limited

Single reported SERPINF2 variant in heterozygous state segregating with disease in one family; absent in 30 controls ([PMID:10583218])

Functional Evidence

Limited

Patient plasma assays show reduced plasmin inhibitor activity (49–66%) and antigenic levels (57–68%) consistent with haploinsufficiency ([PMID:10583218])