2013/07/10 by Samuel D. Quaynor, Earl W. Stradtman, Hyung‐Goo Kim +4 · 3 citations
Biochemistry, Genetics and Molecular Biology · #Estrogen and related hormone effects #Sexual Differentiation and Disorders #Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
paper · pdf · doi:10.1056/nejmoa1303611
openalex publication_date 2013/07/10 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Although androgen resistance has been characterized in men with a normal chromosome complement and mutations in the androgen-receptor gene, a mutation in the gene encoding estrogen receptor α (ESR1) was previously described only in one man and not, to our knowledge, in a woman. We now describe an 18-year-old woman without breast development and with markedly elevated serum levels of estrogens and bilateral multicystic ovaries. She was found to have a homozygous loss-of-function ESR1 mutation in a completely conserved residue that interferes with estrogen signaling. Her clinical presentation was similar to that in the mouse orthologue knockout. This case shows that disruption of ESR1 causes profound estrogen resistance in women. (Funded by the National Institutes of Health.).