title: Deficiency of the human complement regulatory protein factor H associated with low levels of component C9.
abstract: We identified a 4-year-old Brazilian boy from a family of Japanese descent and history of consanguinity, who suffered from severe recurrent pneumonia. He carries factor H (FH) deficiency associated with reduced levels of component C9 and low serum levels of C3 and factor B. His mother also presented low levels of these proteins and factor I, while his father and sister had only lower levels of FH. Western blot assays confirmed the complete absence of FH and FHL-1 polypeptides in this patient. Sequencing of the proband's FH cDNA revealed a homozygous G453A substitution, encoding an Arg(127)His change. His mother, father and sister are heterozygous for this substitution. Despite the absence of FH in the plasma, this protein was detected in the patient's fibroblasts, suggesting that Arg(127) may be important for FH secretion. Low concentrations of C9 were detected in the proband serum but no mutations in the patient's C9 gene or promoter have been identified, suggesting that this is a consequence of uncontrolled complement activation and high C9 consumption.
authors.affiliation: Laboratório de Complemento, Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
authors.forename: D A
authors.initials: DA
authors.lastname: Falcão
authors.forename: E S
authors.initials: ES
authors.lastname: Reis
authors.forename: D
authors.initials: D
authors.lastname: Paixão-Cavalcante
authors.forename: M T
authors.initials: MT
authors.lastname: Amano
authors.forename: M I M V
authors.initials: MI
authors.lastname: Delcolli
authors.forename: M P C
authors.initials: MP
authors.lastname: Florido
authors.forename: J A T
authors.initials: JA
authors.lastname: Albuquerque
authors.forename: D
authors.initials: D
authors.lastname: Moraes-Vasconcelos
authors.forename: A J
authors.initials: AJ
authors.lastname: Duarte
authors.forename: A S
authors.initials: AS
authors.lastname: Grumach
authors.forename: L
authors.initials: L
authors.lastname: Isaac
mesh_terms: D001483:Base Sequence; D025861:Blood Coagulation Disorders, Inherited / Q000097:blood* / Q000235:genetics* / Q000503:physiopathology; D015153:Blotting, Western; D002675:Child, Preschool; D003167:Complement Activation / Q000502:physiology; D003180:Complement C3b Inactivator Proteins; D003186:Complement C9 / Q000032:analysis* / Q000235:genetics; D017242:Complement Factor H / Q000172:deficiency* / Q000235:genetics*; D003165:Complement System Proteins / Q000032:analysis; D003241:Consanguinity; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D009154:Mutation; D010375:Pedigree; D011014:Pneumonia / Q000209:etiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D003186:Complement C9; D017242:Complement Factor H; D003165:Complement System Proteins