Rapid genome sequencing identifies novel variants in complement factor I

Area of Science:

• Immunology
• Genetics
• Infectious Diseases

Background:

• Complement Factor I Deficiency (CFID) is a rare primary immunodeficiency.
• CFID results from insufficient levels of complement factor I (CFI), a serine protease.
• Patients with CFID are highly susceptible to severe infections, particularly from Streptococcus pneumoniae, often presenting in infancy.

Purpose of the Study:

• To describe a case of a previously healthy adolescent male presenting with severe pneumococcal pneumonia and systemic inflammatory response.
• To identify the genetic cause of Complement Factor I Deficiency in this patient.
• To characterize novel variants within the CFI gene.

Main Methods:

• Clinical presentation of an adolescent male with respiratory failure due to pneumococcal pneumonia.
• Utilized rapid genome sequencing (rGS) for genetic analysis.
• Identified and characterized compound heterozygous variants in the CFI gene.

Main Results:

• The proband was diagnosed with Complement Factor I Deficiency.
• Genetic analysis revealed compound heterozygous variants in the CFI gene.
• A novel maternally inherited likely pathogenic variant (c.1646del; p.Asn549ThrfsTer25) and a paternally inherited likely pathogenic deletion (Chr 4:110685580-110692197del) were identified.

Conclusions:

• This case highlights a rare presentation of CFID in adolescence.
• Rapid genome sequencing is effective in diagnosing rare immunodeficiencies.
• The identified novel CFI variants contribute to understanding the genetic basis of CFID.