Clinical and population genetic insights into primary complement component 2 (C2) deficiency: A founder variant in Ashkenazi Jews.
Oded Shamriz, Vered Molho-Pessach, Stephanie Benshushan et al.
✦ AI-curated · Sources linked
Case in brief
A 14-year-old Ashkenazi Jewish boy presented with bullous cutaneous lupus erythematosus and lupus nephritis. His diagnosis of complement component 2 deficiency (C2D) was influenced by a family history of fatal pneumococcal meningitis in a sibling. Genetic testing revealed homozygosity for the C2 c.841_849+19del variant, with complement studies showing absent classical pathway activity and significantly reduced C2 levels.
What made this case unusual
The case highlights a founder variant in the Ashkenazi Jewish population, with a carrier frequency of approximately 3%, which is notably absent in Mizrahi Jews and not detected among Israeli Arabs.
Diagnostic / clinical pearl
Clinicians should consider complement component 2 deficiency in patients with autoimmune manifestations and a relevant family history, particularly in populations with known founder variants.
Why it matters
This case underscores the potential for underdiagnosis of C2D, especially in specific ethnic groups, emphasizing the importance of genetic screening in at-risk populations.