Factor XII deficiency: a clinical and molecular genetic study

Area of Science:

• Genetics
• Hematology
• Molecular Biology

Background:

• Factor XII (FXII) deficiency is a rare inherited coagulation disorder.
• FXII deficiency can manifest with thrombotic or hemorrhagic symptoms, though often asymptomatic.
• Understanding F12 gene mutations is crucial for diagnosing and managing FXII deficiency.

Purpose of the Study:

• To characterize the spectrum of F12 gene mutations in the Russian population.
• To investigate the association between F12 variants and clinical phenotypes.
• To clarify the prevalence of hemorrhagic manifestations in FXII deficiency.

Main Methods:

• Genetic analysis of the F12 gene in 33 patients with FXII deficiency and 26 healthy controls.
• Identification and characterization of F12 gene mutations and variants.
• Correlation of identified F12 variants with patient clinical data.

Main Results:

• Forty mutant alleles and six distinct deleterious F12 substitutions were identified in the Russian cohort.
• Three major F12 substitutions (c.-62C>T, c.-57G>C, c.1532-1G>A) accounted for 92.5% of mutations in this population.
• Three rare, novel F12 substitutions (p.615 del C, c.1180_1181delCA, p.Tyr218His) were also identified.
• Eight patients with mild FXII deficiency were homozygous for the C46T hypomorphic variant without other deleterious mutations.
• Mild hemorrhagic manifestations were frequently observed in patients with FXII deficiency, contrary to existing literature.

Conclusions:

• The study identified key F12 gene mutations prevalent in the Russian population.
• A significant proportion of FXII deficiency cases in Russia are attributable to three specific F12 mutations.
• Mild hemorrhagic symptoms are a common clinical feature of FXII deficiency, challenging previous assumptions.