title: Delayed puberty and estrogen resistance in a woman with estrogen receptor α variant.
abstract: 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.).
authors.affiliation: Section of Reproductive Endocrinology, Infertility, and Genetics, Department of Obstetrics and Gynecology, Institute of Molecular Medicine and Genetics, and the Neuroscience Program, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Quaynor
authors.forename: Earl W
authors.initials: EW
authors.lastname: Stradtman
authors.forename: Hyung-Goo
authors.initials: HG
authors.lastname: Kim
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
authors.forename: Lynn P
authors.initials: LP
authors.lastname: Chorich
authors.forename: Derek A
authors.initials: DA
authors.lastname: Schreihofer
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Layman
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000032:analysis; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood*; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D004970:Estrone / Q000097:blood; D005260:Female; D006801:Humans; D020125:Mutation, Missense; D011628:Puberty, Delayed / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D001786:Blood Glucose; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D004970:Estrone; D004958:Estradiol