C1QB – C1q Deficiency

C1q deficiency is an autosomal recessive immune disorder characterized by absent classical complement activity and predisposition to systemic lupus erythematosus and recurrent infections. Biallelic variants in C1QB abrogate assembly or expression of the C1q B chain, leading to complete loss of functional C1q.

Genetic evidence supports autosomal recessive inheritance with 9 probands across five unrelated families and segregation in two additional affected relatives (PMID:9476130; PMID:17513176). Reported mutations include start‐loss c.3G>T (p.Met1Ile) in a Moroccan kindred (PMID:9476130), canonical splice c.181+1G>T in a Japanese patient (PMID:24160257), and missense c.724G>A (p.Gly242Arg) in an Inuit family (PMID:17513176). The variant spectrum comprises start‐loss, splice, missense and non‐coding splice defects, all yielding loss of C1q B chain function.

Functional assays demonstrate low molecular weight C1q and disrupted collagen‐like assembly by ultracentrifugation in Moroccan cases (PMID:9476130), absence of C1qB mRNA and protein in patient cells by qPCR and Western blot (PMID:25454803), and undetectable serum C1q with abrogated hemolytic activity in Inuit patients (PMID:17513176). These data converge on a loss‐of‐function mechanism.

No conflicting evidence has been reported.

In summary, biallelic LOF variants in C1QB definitively cause autosomal recessive C1q deficiency, with consistent genetic and experimental evidence. This association supports molecular diagnosis, carrier screening, and informs complement replacement therapy.

Key Take-home: Biallelic LOF C1QB variants cause autosomal recessive C1q deficiency, a clinically actionable complement disorder.

References

• Immunopharmacology • 1997 • Molecular basis of a new type of C1q-deficiency associated with a non-functional low molecular weight (LMW) C1q: parallels and differences to other known genetic C1q-defects. PMID:9476130
• Pediatric rheumatology online journal • 2013 • The identification of a novel splicing mutation in C1qB in a Japanese family with C1q deficiency: a case report. PMID:24160257
• Lupus • 2013 • Systemic lupus erythematosus due to C1q deficiency with progressive encephalopathy, intracranial calcification and acquired moyamoya cerebral vasculopathy. PMID:23651859
• Immunobiology • 2015 • Identification of a novel non-coding mutation in C1qB in a Dutch child with C1q deficiency associated with recurrent infections. PMID:25454803
• Clinical immunology • 2007 • C1q deficiency in an Inuit family: identification of a new class of C1q disease-causing mutations. PMID:17513176

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