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Journal of Clinical Immunology

, Volume 36, Issue 4, pp 388–396 | Cite as

Novel Mutations Causing C5 Deficiency in Three North-African Families

  • Roger ColobranEmail author
  • Clara Franco-Jarava
  • Andrea Martín-Nalda
  • Neus Baena
  • Elisabeth Gabau
  • Natàlia Padilla
  • Xavier de la Cruz
  • Ricardo Pujol-Borrell
  • David Comas
  • Pere Soler-Palacín
  • Manuel Hernández-González
Original Article

Abstract

The complement system plays a central role in defense to encapsulated bacteria through opsonization and membrane attack complex (MAC) dependent lysis. The three activation pathways (classical, lectin, and alternative) converge in the cleavage of C5, which initiates MAC formation and target lysis. C5 deficiency is associated to recurrent infections by Neisseria spp. In the present study, complement deficiency was suspected in three families of North-African origin after one episode of invasive meningitis due to a non-groupable and two uncommon Meningococcal serotypes (E29, Y). Activity of alternative and classical pathways of complement were markedly reduced and the measurement of terminal complement components revealed total C5 absence. C5 gene analysis revealed two novel mutations as causative of the deficiency: Family A propositus carried a homozygous deletion of two adenines in the exon 21 of C5 gene, resulting in a frameshift and a truncated protein (c.2607_2608del/p.Ser870ProfsX3 mutation). Families B and C probands carried the same homozygous deletion of three consecutive nucleotides (CAA) in exon 9 of the C5 gene, leading to the deletion of asparagine 320 (c.960_962del/p.Asn320del mutation). Family studies confirmed an autosomal recessive inheritance pattern. Although sharing the same geographical origin, families B and C were unrelated. This prompted us to investigate this mutation prevalence in a cohort of 768 North-African healthy individuals. We identified one heterozygous carrier of the p.Asn320del mutation (allelic frequency = 0.065 %), indicating that this mutation is present at low frequency in North-African population.

Keywords

Complement system complement 5 deficiency meningococcal disease mutation African continental ancestry group 

Notes

Acknowledgements

We are deeply grateful to all the affected individuals and their families who participated in this study. This study was funded by Instituto de Salud Carlos III, grant PI14/00405, cofinanced by the European Regional Development Fund (ERDF), and by MINECO grant CGL2013-44351-P. We thank Karima Fadhlaoui-Zid for providing some North-African DNA samples.

Compliance with Ethical Standards

Conflicts of Interest

None of the authors has any potential financial conflict of interest related to this manuscript.

Supplementary material

10875_2016_275_MOESM1_ESM.pdf (2.9 mb)
ESM 1 (PDF 3005 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Roger Colobran
    • 1
    • 2
    Email author
  • Clara Franco-Jarava
    • 1
  • Andrea Martín-Nalda
    • 3
  • Neus Baena
    • 4
  • Elisabeth Gabau
    • 4
  • Natàlia Padilla
    • 5
  • Xavier de la Cruz
    • 5
  • Ricardo Pujol-Borrell
    • 1
  • David Comas
    • 6
  • Pere Soler-Palacín
    • 3
  • Manuel Hernández-González
    • 1
  1. 1.Immunology Division, Hospital Universitari Vall d’Hebron (HUVH), Vall d’Hebron Research Institute (VHIR)Universitat Autònoma de Barcelona (UAB)BarcelonaSpain
  2. 2.Immunology Division, Hospital Universitari Vall d’Hebron (HUVH), Vall d’Hebron Research Institute (VHIR)Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB)BarcelonaSpain
  3. 3.Pediatric Infectious Diseases and Immunodeficiencies Unit (UPIIP), Hospital Universitari Vall d’Hebron (HUVH), Vall d’Hebron Research Institute (VHIR)Universitat Autònoma de Barcelona (UAB)BarcelonaSpain
  4. 4.Genetic Laboratory UDIAT-Diagnostic CenterCorporació Sanitària Parc TaulíSabadellSpain
  5. 5.Research Unit in Translational Bioinformatics, Vall d’Hebron Research Institute (VHIR)Universitat Autònoma de Barcelona (UAB)BarcelonaSpain
  6. 6.Departament de Ciències Experimentals i de la Salut, Institut de Biologia Evolutiva (CSIC-UPF)Universitat Pompeu FabraBarcelonaSpain

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