Complement 4 phenotypes and genotypes in Brazilian patients with classical 21-hydroxylase deficiency

Autor(es)

Guerra-Junior, G. ^[1] ; Grumach, A. Sevciovic ^[2] ; de Lemos-Marini, S. H. Valente ^[3] ; Kirschfink, M. ^[4] ; Condino Neto, A. ^[5] ; de Araujo, M. ^[6] ; De Mello, M. Palandi ^[6]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Dept Pediat, Fac Med Sci, BR-13083970 Campinas, SP - Brazil

^[2] Univ Sao Paulo, Sch Med, Lab Med Investigat Dermatol & Immunodeficiencies, Sao Paulo - Brazil

^[3] Univ Estadual Campinas, Ctr Investigat Pediat CIPED, BR-13083970 Campinas, SP - Brazil

^[4] Univ Heidelberg, Inst Immunol, D-6900 Heidelberg - Germany

^[5] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

^[6] Univ Estadual Campinas, Ctr Mol Biol & Genet Engn CBMEG, BR-13083970 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CLINICAL AND EXPERIMENTAL IMMUNOLOGY; v. 155, n. 2, p. 182-188, FEB 2009.
• Citações Web of Science: 1

Resumo

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 monomodular 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. (AU)

• Processo FAPESP: 97/07622-2 - Caracterização molecular de alelos raros relacionados com a deficiência da 21-hidroxilase
• Beneficiário: Maricilda Palandi de Mello
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 92/03332-6 - Identificação e caracterização de mutações relativas à deficiência da 21-hidroxilase em 21 famílias
• Beneficiário: Maricilda Palandi de Mello
• Modalidade de apoio: Auxílio à Pesquisa - Regular