A Novel Mutation in the Complement Component 3 Gene in a Patient with Selective IgA Deficiency

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ORIGINAL RESEARCH

A Novel Mutation in the Complement Component 3 Gene in a Patient with Selective IgA Deficiency Elisangela Santos-Valente & Ismail Reisli & Hasibe Artaç & Raphael Ott & Özden Sanal & Kaan Boztug

Received: 3 July 2012 / Accepted: 21 August 2012 / Published online: 21 September 2012 # The Author(s) 2012. This article is published with open access at Springerlink.com

Abstract Purpose Immunological and molecular evaluation of a patient presenting with recurrent infections caused by Streptococcus pneumoniae and low complement component 3 (C3) levels. Methods Immunological evaluation included complement components and immunoglobulin level quantification as well as number and function of T cells, B cells and neutrophils. Serotype-specific immunoglobulin G antibodies against S. pneumoniae capsular polysaccharides were quantified by ELISA in serum samples before and after vaccination with unconjugated polysaccharide vaccine. For the molecular analysis, genomic DNA from the patient and parents were isolated and all exons as well as exon-intron

boundaries of the C3 gene were sequenced by Sanger sequencing. Results A 16-year-old male, born to consanguineous parents, presented with recurrent episodes of pneumonia caused by S. pneumoniae and bronchiectasis. The patient showed severely reduced C3 and immunoglobulin A levels, while the parents showed moderately reduced levels of C3. Mutational analysis revealed a novel, homozygous missense mutation in the C3 gene (c. C4554G, p. Cys1518Trp), substituting a highly conserved amino acid in the C345C domain of C3 and interrupting one of its disulfide bonds. Both parents were found to be carriers of the affected allele. Vaccination against S. pneumoniae resulted in considerable clinical improvement.

Elisangela Santos-Valente and Ismail Reisli contributed equally and should be considered aequo loco. Electronic supplementary material The online version of this article (doi:10.1007/s10875-012-9775-z) contains supplementary material, which is available to authorized users. E. Santos-Valente : R. Ott : K. Boztug (*) CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3, A-1090 Vienna, Austria e-mail: [email protected]

H. Artaç Department of Pediatric Immunology and Allergy, Selçuk University Selçuklu Medical Faculty, Alaeddin Keykubat Kampusu, 42075 Konya, Turkey Ö. Sanal Immunology Division, Hacettepe University, Children’s Hospital, 06100 Sihhiye, Ankara, Turkey

I. Reisli (*) Meram Medical Faculty, Department of Pediatric Immunology, Necmettin Erbakan University, Beysehir Yolu, 42080 Konya, Turkey e-mail: [email protected]

K. Boztug Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria

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Conclusions We report a novel homozygous mutation in the C3 gene in a patient with concomitant selective IgA deficiency who presented with a marked clinical improvement after vaccination against S. pneumoniae. This observation underlines the n

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A Novel Mutation in the Complement Component 3 Gene in a Patient with Selective IgA Deficiency

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