Female Pseudohermaphroditism Caused by a Novel Homozygous Missense Mutation of the GR Gene

The study described a novel case of female pseudohermaphroditism caused by a homozygous missense mutation in the GR gene, leading to glucocorticoid resistance. The patient, born with ambiguous genitalia, exhibited severe hypokalemia and high levels of ACTH, cortisol, androstenedione, testosterone, and 17-hydroxyprogesterone, which were inconsistent with classic congenital adrenal hyperplasia. Genetic analysis revealed a T to C substitution at nucleotide 1844 in exon 5 of the GR gene, resulting in a valine to alanine substitution at amino acid 571, significantly reducing receptor binding affinity and trans-activation activity. This case highlighted that pre- and postnatal virilization can occur in females with glucocorticoid resistance syndrome.