A pedigree analysis of deep venous thrombosis caused by rare compound heterozygous PROC mutations combined with a heterozygous THBD mutation

Venous thromboembolism is a common fatal disease that includes pulmonary embolism (PE) and deep vein thrombosis (DVT), and many genetic risk factors are associated with its pathogenesis. We describe a patient with compound heterozygous mutations in PROC combined with a heterozygous mutation in THBD, who was diagnosed with DVT. Genetic sequencing identified three missense mutations in the proband: PROC c.565 C > T (p.R189W), PROC c.1218G > A (p.M406I), and THBD c.1456G > T (p.D486Y), this genotype not previously documented in association with thrombotic disease. His father carried heterozygous mutations of PROC p.R189W and THBD p.D486Y, while his mother and maternal grandfather were heterozygous for PROC p.M406I. These mutations were not detected in other family members.