title: Primary complement C5 deficiencies - molecular characterization and clinical review of two families.
abstract: Inherited deficiency states of the terminal complement component C5 are rare and often associated with increased risk of recurrent Neisseria infections. More than 50 cases with primary C5 deficiency have been reported. In spite of this, the molecular basis has only been documented in a few cases. In the present study we investigated two unrelated Caucasian probands with C5 deficiency originating from Norway and Denmark, respectively, and found three previously undescribed mutations. With these data, thirteen mutations associated with C5 deficiency have been described. By genetic screening of the family of the Norwegian patient, previously diagnosed as homozygous C5 deficient and suffering four Neisseria infections, an additional case of C5 deficiency was discovered, who had experienced one episode of Neisseria infections. Detailed review of the clinical history of the patients and their healthy relatives did not reveal any differences between C5 deficient and sufficient individuals with regard to clinical presentation, apart from the susceptibility to Neisseria infections. Of note, one of the patients described here, and several C5 deficient patients from the literature had Neisseria meningitidis serotype B infections, which is not covered by the current vaccines. These data support the clinical guidelines for patients treated with C5 inhibitors, who are functional C5 deficient by the treatment.
authors.affiliation: Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark. Lone.Schejbel.Dupont@regionh.dk
authors.forename: Lone
authors.initials: L
authors.lastname: Schejbel
authors.forename: Dag
authors.initials: D
authors.lastname: Fadnes
authors.forename: Henrik
authors.initials: H
authors.lastname: Permin
authors.forename: Knut Tore
authors.initials: KT
authors.lastname: Lappegård
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
authors.forename: Tom Eirik
authors.initials: TE
authors.lastname: Mollnes
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003182:Complement C5 / Q000235:genetics*; D004252:DNA Mutational Analysis; D003718:Denmark; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009343:Neisseria / Q000276:immunology*; D009664:Norway; D010375:Pedigree; D017410:Practice Guidelines as Topic; D012306:Risk; D044465:White People
chemical_list: D003182:Complement C5
keywords: C5; Complement; Deficiency; Meningococcal infection