title: Complement component C7 deficiency in two Spanish families.
abstract: Different genetic mutations have been described in complement component C7 deficiency, a molecular defect clinically associated with an increased susceptibility to neisserial recurrent infections. In this work we report the genetic basis of C7 deficiency in two different Spanish families (family 1 and family 2). In family 1, of Gypsy ethnical background, exon-specific polymerase chain reaction and sequencing revealed a not previously described single base deletion of nucleotide 1309 (exon 10) in the patient, as well as in her father, leading to a stop codon that causes the premature truncation of the C7 protein (K416 X 419). Additionally, the patient and her mother displayed a missense mutation at position 1135 (exon 9) located in the first nucleotide of the codon GGG (CGG), resulting in a change of amino acid (G357R). This mutation was firstly described in individuals of Moroccan Sephardic Jewish ancestry and has been also reported among Spaniards. In family 2, another novel mutation was found in homozygosity in two siblings; a two base-pair deletion of nucleotides 1922 and 1923 in exon 14 leading to the generation of a downstream stop codon causing the truncation of the C7 protein product (S620 X 630). Our results provide more evidence for the heterogeneous molecular basis of C7 deficiency as well as for the subsequent susceptibility to meningococcal disease, since different families carry different molecular defects. On the other hand, certain C7 defects appear to be prevalent in individuals from certain populations or living in defined geographical areas.
authors.affiliation: Servicio de Inmunología, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Barroso
authors.forename: Berta
authors.initials: B
authors.lastname: Sánchez
authors.forename: Antonia José
authors.initials: AJ
authors.lastname: Alvarez
authors.forename: Margarita
authors.initials: M
authors.lastname: López-Trascasa
authors.forename: Amparo
authors.initials: A
authors.lastname: Lanuza
authors.forename: Rafael
authors.initials: R
authors.lastname: Luque
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Wichmann
authors.forename: Antonio
authors.initials: A
authors.lastname: Núñez-Roldán
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D003184:Complement C7 / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008589:Meningococcal Infections / Q000276:immunology; D008969:Molecular Sequence Data; D009894:Opportunistic Infections / Q000276:immunology; D010375:Pedigree; D017354:Point Mutation
chemical_list: D003184:Complement C7