Complement factor I deficiency: a not so rare immune defect. Characterization of new mutations and the first large gene deletion

Orphanet Journal of Rare Diseases - 2012
María Alba‐Domínguez1, Alberto López‐Lera1, Sofía Garrido1, Pilar Nozal1, Ignacio González-Granado2, Josefa Melero3, Pere Soler‐Palacín4, Carmen Cámara5, Margarita López-Trascasa6
1Unidad de Inmunología Hospital Universitario La Paz and Hospital La Paz Health Research Institute (IdiPAZ), Madrid, Spain
2Departamento de Pediatría Hospital Universitario 12 de Octubre, Madrid, Spain
3Servicio Inmunología Hospital Infanta Cristina, Badajoz, Spain
4Unidad de Patología Infecciosa e Inmunodeficiencias de Pediatría. Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
5Servicio Inmunología Hospital San Pedro de Alcántara, Cáceres, Spain
6Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain

Tóm tắt

AbstractBackgroundComplement Factor I (CFI) is a serine protease with an important role in complement alternative pathway regulation. Complete factor I deficiency is strongly associated with severe infections. Approximately 30 families with this deficiency have been described worldwide.Patients and methodsWe have studied five new Spanish families suffering from CFI deficiency. From 19 screened people, 7 homozygous, 10 heterozygous and 2 healthy subjects were identified. Clinical, biochemical and genetic descriptions are included.ResultsMolecular studies demonstrated 4 novel mutations in the screened individuals; amongst them, we describe here the first great gene deletion reported in the CFI locus, which includes full exon 2 and part of the large intron 1.ConclusionCFI deficiency is possibly an underestimated defect and the eventual existence of this deficiency should be tested in those patients exhibiting low C3 and recurrent bacterial infections. We propose a simple diagnostic flowchart to help clinicians in the identification and correct diagnosis of such patients.

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