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Summary objective Abnormal corticosteroid-binding globulin (CBG) is an extremely rare condition and only three mutations have been described in four families. The molecular basis of an abnormal CBG in a Brazilian family was studied and correlations between genotype and serum cortisol, cortisol binding capacity (CBC) and CBG levels were determined. subjects All 10 family members, comprising three generations, and nine healthy volunteers were studied. measurements Genomic DNA was extracted from white blood cells from all family members. The human cbg exons 2–5 were amplified by PCR, submitted to automatic sequencing. Cortisol and CBG levels in serum were measured by radioimmunoassay (RIA). CBC in serum was determined using tritiated cortisol and other cortisol binding parameters were calculated through Scatchard analysis. results A missense mutation in exon 5 of cbg (1254G → A; Asp367Asn), recently described as CBG Lyon, was found in all family members. The proband and one sister were homozygous whereas all other family members, including parents, were heterozygous for this mutation. Cortisol levels in the only two homozygotes were lower than in heterozygotes and both were significantly lower as compared to controls (69 and 182 nmol/l vs. 267 ± 129 nmol/l vs. 459 ± 195 nmol/l, respectively, P |
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