title: Homozygous hereditary C3 deficiency due to a premature stop codon.
abstract: C3 deficiency in humans is a rare disorder characterized by severe recurrent infections. We identified the mutations responsible for a complete homozygous C3 deficiency. Sequencing of the proband C3 cDNA (5067 bp) revealed the following alterations: (a) a silent G-->A transition at nucleotide 972; (b) a T-->C substitution at nucleotide 1001 resulting in a L314P transition; and (c) a stop codon in exon 13 caused by a G-->A substitution at position 1716. The presence of the same premature termination codon was confirmed in approximately half the clones obtained from the proband's paternal and maternal genomic DNAs. Finally, the proband produced approximately 20-fold less C3 mRNA than the normal control. Therefore, in addition to the fact that no functional protein will be synthesized in the deficient cells, this nonsense mutation may be associated with the low C3 mRNA levels.
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
authors.forename: Edimara
authors.initials: E
authors.lastname: Da Silva Reis
authors.forename: Gisele Vanessa
authors.initials: GV
authors.lastname: Baracho
authors.forename: Adriana
authors.initials: A
authors.lastname: Sousa Lima
authors.forename: Chuck S
authors.initials: CS
authors.lastname: Farah
authors.forename: Lourdes
authors.initials: L
authors.lastname: Isaac
mesh_terms: D000293:Adolescent; D002478:Cells, Cultured; D018389:Codon, Nonsense / Q000235:genetics*; D003176:Complement C3 / Q000032:analysis / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018389:Codon, Nonsense; D003176:Complement C3; D018076:DNA, Complementary; D012333:RNA, Messenger