Identification of novel coding mutation in C1qA gene in an African-American pedigree with lupus and C1q deficiency

B. Namjou, M. Keddache, D. Fletcher, S. Dillon, L. Kottyan, G. Wiley, P. M. Gaffney, B. E. Wakeland, C. Liang, E. K. Wakeland, R. H. Scofield, K. Kaufman, J. B. Harley

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Objectives: Homozygous C1q deficiency is an extremely rare condition and strongly associated with systemic lupus erythematosus. To assess and characterize C1q deficiency in an African-American lupus pedigree, C1q genomic region was evaluated in the lupus cases and family members. Methods: Genomic DNA from patient was obtained and C1q A, B and C gene cluster was sequenced using next generation sequencing method. The identified mutation was further confirmed by direct Sanger sequencing method in the patient and all blood relatives. C1q levels in serum were measured using sandwich ELISA method. Results: In an African-American patient with lupus and C1q deficiency, we identified and confirmed a novel homozygote start codon mutation in C1qA gene that changes amino acid methionine to arginine at position 1. The Met1Arg mutation prevents protein translation (Met1Arg). Mutation analyses of the patient's family members also revealed the Met1Arg homozygote mutation in her deceased brother who also had lupus with absence of total complement activity consistent with a recessive pattern of inheritance. Conclusion: The identification of new mutation in C1qA gene that disrupts the start codon (ATG to AGG (Met1Arg)) has not been reported previously and it expands the knowledge and importance of the C1q gene in the pathogenesis of lupus especially in the high-risk African-American population.

Original languageEnglish (US)
Pages (from-to)1113-1118
Number of pages6
JournalLupus
Volume21
Issue number10
DOIs
StatePublished - Sep 2012

Fingerprint

Pedigree
African Americans
Mutation
Genes
Initiator Codon
Homozygote
Inheritance Patterns
Protein Biosynthesis
Multigene Family
Methionine
Systemic Lupus Erythematosus
Arginine
Siblings
Enzyme-Linked Immunosorbent Assay
Amino Acids
DNA
Serum
Population

Keywords

  • C1q (complement)
  • nephritis
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Rheumatology

Cite this

Namjou, B., Keddache, M., Fletcher, D., Dillon, S., Kottyan, L., Wiley, G., ... Harley, J. B. (2012). Identification of novel coding mutation in C1qA gene in an African-American pedigree with lupus and C1q deficiency. Lupus, 21(10), 1113-1118. https://doi.org/10.1177/0961203312443993

Identification of novel coding mutation in C1qA gene in an African-American pedigree with lupus and C1q deficiency. / Namjou, B.; Keddache, M.; Fletcher, D.; Dillon, S.; Kottyan, L.; Wiley, G.; Gaffney, P. M.; Wakeland, B. E.; Liang, C.; Wakeland, E. K.; Scofield, R. H.; Kaufman, K.; Harley, J. B.

In: Lupus, Vol. 21, No. 10, 09.2012, p. 1113-1118.

Research output: Contribution to journalArticle

Namjou, B, Keddache, M, Fletcher, D, Dillon, S, Kottyan, L, Wiley, G, Gaffney, PM, Wakeland, BE, Liang, C, Wakeland, EK, Scofield, RH, Kaufman, K & Harley, JB 2012, 'Identification of novel coding mutation in C1qA gene in an African-American pedigree with lupus and C1q deficiency', Lupus, vol. 21, no. 10, pp. 1113-1118. https://doi.org/10.1177/0961203312443993
Namjou, B. ; Keddache, M. ; Fletcher, D. ; Dillon, S. ; Kottyan, L. ; Wiley, G. ; Gaffney, P. M. ; Wakeland, B. E. ; Liang, C. ; Wakeland, E. K. ; Scofield, R. H. ; Kaufman, K. ; Harley, J. B. / Identification of novel coding mutation in C1qA gene in an African-American pedigree with lupus and C1q deficiency. In: Lupus. 2012 ; Vol. 21, No. 10. pp. 1113-1118.
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