Molecular basis of hereditary C1q deficiency associated with SLE and IgA nephropathy in a Turkish family

R Topaloglu, A Bakkaloglu, JH Slingsby, MJ Mihatsch, M Pascual, P Norsworthy, Bernard J Morley, U Saatci, JA Schifferli, MJ Walport

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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 stale. 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.
Original languageEnglish
Pages (from-to)635-642
Number of pages8
JournalKidney International
Volume50
Issue number2
DOIs
Publication statusPublished - Aug 1996

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Immunoglobulin A
Hepatitis B Vaccines
Mutation
Hematuria
Antibody Formation
Classical Complement Pathway
Nonsense Codon
DNA
Disease Susceptibility
Glomerulonephritis
Exanthema
Proteinuria
Point Mutation
Codon
Genes
Siblings
Parents
Kidney
Biopsy
Polymerase Chain Reaction

Cite this

Topaloglu, R., Bakkaloglu, A., Slingsby, JH., Mihatsch, MJ., Pascual, M., Norsworthy, P., ... Walport, MJ. (1996). Molecular basis of hereditary C1q deficiency associated with SLE and IgA nephropathy in a Turkish family. Kidney International, 50(2), 635-642. https://doi.org/10.1038/ki.1996.359

Molecular basis of hereditary C1q deficiency associated with SLE and IgA nephropathy in a Turkish family. / Topaloglu, R; Bakkaloglu, A; Slingsby, JH; Mihatsch, MJ; Pascual, M; Norsworthy, P; Morley, Bernard J; Saatci, U; Schifferli, JA; Walport, MJ.

In: Kidney International, Vol. 50, No. 2, 08.1996, p. 635-642.

Research output: Contribution to journalArticle

Topaloglu, R, Bakkaloglu, A, Slingsby, JH, Mihatsch, MJ, Pascual, M, Norsworthy, P, Morley, BJ, Saatci, U, Schifferli, JA & Walport, MJ 1996, 'Molecular basis of hereditary C1q deficiency associated with SLE and IgA nephropathy in a Turkish family', Kidney International, vol. 50, no. 2, pp. 635-642. https://doi.org/10.1038/ki.1996.359
Topaloglu R, Bakkaloglu A, Slingsby JH, Mihatsch MJ, Pascual M, Norsworthy P et al. Molecular basis of hereditary C1q deficiency associated with SLE and IgA nephropathy in a Turkish family. Kidney International. 1996 Aug;50(2):635-642. https://doi.org/10.1038/ki.1996.359
Topaloglu, R ; Bakkaloglu, A ; Slingsby, JH ; Mihatsch, MJ ; Pascual, M ; Norsworthy, P ; Morley, Bernard J ; Saatci, U ; Schifferli, JA ; Walport, MJ. / Molecular basis of hereditary C1q deficiency associated with SLE and IgA nephropathy in a Turkish family. In: Kidney International. 1996 ; Vol. 50, No. 2. pp. 635-642.
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