title: Complement 4 phenotypes and genotypes in Brazilian patients with  classical 21-hydroxylase deficiency.
abstract: The aim of this work was to analyse C4 genotypes, C4 protein levels, phenotypes and genotypes in patients with the classical form of 21-hydroxylase deficiency. Fifty-four patients from 46 families (36 female, 18 male; mean age 10.8 years) with different clinical manifestations (31 salt-wasting; 23 simple-virilizing) were studied. Taq I Southern blotting was used to perform molecular analysis of the C4/CYP21 gene cluster and the genotypes were defined according to gene organization within RCCX modules. Serum C4 isotypes were assayed by enzyme-linked immunosorbent assay. The results revealed 12 different haplotypes of the C4/CYP21 gene cluster. Total functional activity of the classical pathway (CH50) was reduced in individuals carrying different genotypes because of low C4 concentrations (43% of all patients) to complete or partial C4 allotype deficiency. Thirteen of 54 patients presented recurrent infections affecting the respiratory and/or the urinary tracts, none of them with severe infections. Low C4A or C4B correlated well with RCCX mono-modular gene organization, but no association between C4 haplotypes and recurrent infections or autoimmunity was observed. Considering this redundant gene cluster, C4 seems to be a well-protected gene segment along the evolutionary process.
authors.affiliation: Department of Pediatrics, Faculty of Medical Sciences, University of Campinas, UNICAMP, Campinas, SP 13083-970, Brazil. gilguer@fcm.unicamp.br
authors.forename: G
authors.initials: G
authors.lastname: Guerra-Junior
authors.forename: A Sevciovic
authors.initials: AS
authors.lastname: Grumach
authors.forename: S H Valente
authors.initials: SH
authors.lastname: de Lemos-Marini
authors.forename: M
authors.initials: M
authors.lastname: Kirschfink
authors.forename: A
authors.initials: A
authors.lastname: Condino Neto
authors.forename: M
authors.initials: M
authors.lastname: de Araujo
authors.forename: M Palandi
authors.initials: MP
authors.lastname: De Mello
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000150:complications / Q000235:genetics* / Q000276:immunology; D001327:Autoimmune Diseases / Q000150:complications; D002648:Child; D002675:Child, Preschool; D003167:Complement Activation / Q000235:genetics / Q000276:immunology; D003181:Complement C4 / Q000032:analysis / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D009894:Opportunistic Infections / Q000150:complications; D010641:Phenotype; D012008:Recurrence; D013255:Steroid 21-Hydroxylase / Q000235:genetics; D055815:Young Adult
chemical_list: D003181:Complement C4; C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase