title: C7 deficiency and meningococcal infection susceptibility in two spanish families.
abstract: In this work, we report the genetic basis of C7 deficiency in two different Spanish families. In family 1, by using exon-specific polymerase chain reaction and sequencing, a recently described mutation was found in homozygosity in the patient; a single base change in exon 15 (C2107T) leading to a stop codon that causes truncation of the C-terminal portion of C7 (Q681X). Patient's father, mother and sister were heterozygous for this mutation. Interestingly, patient's parents were not related. In family 2, a new single base mutation in exon 2 (G90A), leading to a stop codon that causes the premature truncation of C7 (W8X), was found in the patient, mother and sister 1. Additionally, patient 2, her father and sisters, displayed a missense mutation in exon 9 (G1135C) resulting in a change of aminoacid (G357R). Although sister 1 bore the same mutations in the C7 gene that patient 2, she remains asymptomatic. Because both mutations were found in the patient and her sister, we analyse other defence mechanisms such as FcgammaR polymorphisms as well as mannose-binding lectin alleles (MBL2 gene) and MBL levels. Results showed that both siblings bore identical combinations of FcgammaR allotypes and different MBL2 alleles, exhibiting patient 2 a MBL-insufficient genotype. Normal MBL levels were found in patient 1 and in two previously studied C7-deficient siblings, suggesting the involvement of other mechanisms of immunity distinct of FcgammaR variants and the MBL pathway, for the absence of meningococcal recurrent infections in certain C7-deficient individuals.
authors.affiliation: Servicio de Inmunología, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Barroso
authors.forename: M
authors.initials: M
authors.lastname: López-Trascasa
authors.forename: D
authors.initials: D
authors.lastname: Merino
authors.forename: A J
authors.initials: AJ
authors.lastname: Alvarez
authors.forename: A
authors.initials: A
authors.lastname: Núñez-Roldán
authors.forename: B
authors.initials: B
authors.lastname: Sánchez
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003184:Complement C7 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000737:chemistry / Q000235:genetics; D008589:Meningococcal Infections / Q000235:genetics* / Q000276:immunology*; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000276:immunology*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000737:chemistry / Q000235:genetics; D013030:Spain
chemical_list: D003184:Complement C7; C489017:FCGR1A protein, human; D037601:Mannose-Binding Lectin; D017452:Receptors, IgG; D004247:DNA