title: Molecular characterization of Complement Factor I deficiency in two Spanish families.
abstract: Complement Factor I (CFI) is a regulator of the classical and alternative pathways. CFI has enzymatic activity and is able to cleave C3b and C4b. Homozygous Factor I deficiency is associated with infectious and/or autoimmune diseases. Here we describe the biochemical and genetic characterization in two Spanish families with complete Factor I deficiency. In Family 1, the propositus suffered from several episodes of meningitis for more than a year. Biochemical complement studies showed undetectable Factor I levels in the propositus and in her sister, while their parents and a brother had partial Factor I deficiency and were healthy. In Family 2, three out of five children were homozygous for Factor I deficiency, two of whom suffered from meningitis and the third one from several infections. The parents and the other two siblings were healthy and heterozygous for Factor I deficiency. Molecular studies showed that the two families had different mutations at exon 5 of the Factor I gene, which codifies for module LDLr1. One mutation corresponds to a 772G>A change at the donor splice site that was originally found in a family from Northern England. The second is a new missense mutation 739T>G, that generates a Cys to Gly change.
authors: Unidad de Inmunología, Hospital Universitario La Paz, Paseo de la Castellana 261, Madrid, Spain.
authors: Isabel María
authors: IM
authors: Ponce-Castro
authors: Carolina
authors: C
authors: González-Rubio
authors: Eva María
authors: EM
authors: Delgado-Cerviño
authors: Cynthia
authors: C
authors: Abarrategui-Garrido
authors: Gumersindo
authors: G
authors: Fontán
authors: Pilar
authors: P
authors: Sánchez-Corral
authors: Margarita
authors: M
authors: López-Trascasa
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D017244:Complement Factor I / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics*; D020451:Contig Mapping; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D005190:Family; D005260:Female; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D017434:Protein Structure, Tertiary; D013030:Spain; D044465:White People / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D017244:Complement Factor I