COPA syndrome caused by a novel p.Arg227Cys COPA gene variant

Area of Science:

• Genetics
• Immunology
• Pediatrics

Background:

• COPA syndrome is a rare, autosomal dominant monogenic disease caused by COPA gene mutations.
• It presents with inflammatory lung, joint, and kidney disease, potentially linked to autophagy and type I interferon pathways.
• Only 59 cases have been reported globally.

Observation:

• A 5-year-old girl presented with arthritis, ANCA-associated vasculitis, and kidney decline, with minimal lung issues.
• Trio-whole exome sequencing identified a novel heterozygous mutation in the COPA gene (c.679C>T, p.Arg227Cys).
• This mutation was maternally inherited, though the mother showed no symptoms.

Findings:

• A novel likely pathogenic heterozygous variation in the COPA gene was identified in a pediatric patient.
• The identified mutation (c.679C>T, p.Arg227Cys) expands the known genetic spectrum of COPA syndrome.
• The case highlights a distinct clinical presentation with prominent vasculitis and renal involvement.

Implications:

• This finding expands the genotypic spectrum of COPA syndrome.
• It provides crucial reference data for future clinical diagnosis and treatment strategies.
• Understanding genotype-phenotype correlations in COPA syndrome is essential for effective management.