title: Molecular basis of hereditary C1q deficiency associated with SLE and IgA nephropathy in a Turkish family.
abstract: Two siblings (case 1 and case 2) with homozygous C1q deficiency are described. Both presented with a photosensitive rash, and during follow-up case one developed SLE with nephrotic range proteinuria. Case 2 had microscopic hematuria with a past history of macroscopic hematuria. Renal biopsies revealed mesangioproliferative glomerulonephritis in case 1 and IgA nephropathy in case 2, a new finding in association with C1q deficiency. Since the classical pathway of complement plays a role in the development of antibody responses, the family was also evaluated for the immune response to hepatitis B vaccine. Antibody response to hepatitis B vaccine was normal in both affected members and the rest of the family. The A-, B- and C- chain genes of C1q were amplified by PCR and directly sequenced. A homozygous C to T point mutation was identified in genomic DNA isolated from the patients at codon 186 in the A chain that resulted in a premature stop codon. This mutation was present in both parents and both unaffected sibs in the heterozygous state. This mutation was identical to that previously described in a Slovakian family with C1q deficiency. Because of this finding, a series of 92 genomic DNA samples was screened from ethnically distinct patient groups with SLE to test the hypothesis that this mutation of C1q may be a widespread disease susceptibility gene. No further examples of this mutation were found.
authors.affiliation: Department of Pediatric Nephrology and Rheumatology, Hacettepe University, Ankara, Turkey.
authors.forename: R
authors.initials: R
authors.lastname: Topaloglu
authors.forename: A
authors.initials: A
authors.lastname: Bakkaloglu
authors.forename: J H
authors.initials: JH
authors.lastname: Slingsby
authors.forename: M J
authors.initials: MJ
authors.lastname: Mihatsch
authors.forename: M
authors.initials: M
authors.lastname: Pascual
authors.forename: P
authors.initials: P
authors.lastname: Norsworthy
authors.forename: B J
authors.initials: BJ
authors.lastname: Morley
authors.forename: U
authors.initials: U
authors.lastname: Saatci
authors.forename: J A
authors.initials: JA
authors.lastname: Schifferli
authors.forename: M J
authors.initials: MJ
authors.lastname: Walport
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D015922:Complement C1q / Q000172:deficiency* / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000150:complications / Q000235:genetics*; D015432:Glomerulonephritis, Membranoproliferative / Q000097:blood / Q000150:complications / Q000235:genetics; D017325:Hepatitis B Vaccines / Q000276:immunology; D006720:Homozygote; D006801:Humans; D007114:Immunization; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications / Q000235:genetics*; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D014421:Turkey
chemical_list: D017931:DNA Primers; D017325:Hepatitis B Vaccines; D015922:Complement C1q