Genetic analysis of antithrombin deficiency among Thai patients with thrombosis

Abstract

Hereditary antithrombin (AT) deficiency, primarily caused by mutations of SERPINC1 mutations, is a strong risk factor for occurrences and recurrences of venous thrombosis. While AT activity level measurements may be interfered by several factors, genetic analysis is more definitive for diagnosis. This study aims to address the knowledge gap of genetic basis of AT deficiency among Thai patients. Samples were collected from patients with thrombosis and low AT activities. Cases with acquired causes of low AT were excluded. All 7 exons of the SERPINC1 gene were PCR amplified and subjected to Sanger sequencing. The study included 15 patients and 6 controls with normal AT activity levels. The results revealed the presence of 6 benign single nucleotide polymorphisms (SNPs) located in intron 1, 2, exon 5 and intron 5. Two of these SNPs in intron 2 were first described here. Notably, a novel SNP in exon 3, SERPINC1 c.570 C>G (p.Y190X), was discovered. This is likely pathogenic because the premature stop codon led to a non-functional protein. The results suggest that pathogenic SERPINC1 variants detectable by DNA sequencing are uncommon among Thai patients with low AT activity levels underscoring the role of genetic analysis for definitive diagnosis. Further studies involving larger numbers of patients are required.