Turek-Plewa J, Starzyk J B, Trzeciak W H
Department of Biochemistry and Molecular Biology, University of Medical Sciences, 6 Swiecickiego St., 60-781, Poznan, Poland.
Department of Pediatric and Adolescent Endocrinology, Polish-American Children's Hospital, Faculty of Medicine, Cracow, Poland.
J Appl Genet. 2015 Nov;56(4):463-467. doi: 10.1007/s13353-015-0288-3. Epub 2015 May 22.
A patient with a female phenotype, 46,XY karyotype, and a diagnosis of complete androgen insensitivity syndrome (CAIS) was examined. Her mother and three 46,XX sisters were also included in the study. Sequence analysis of the androgen receptor gene (AR) revealed a novel A2933 insertion that alters the Tyr codon to a termination codon (Y857X), resulting in a truncated form of the receptor. Computer simulation revealed major conformational changes in the hydrophobic pocket that accommodates the hormone. An insA2933 results in a truncated receptor incapable of binding the ligand and is responsible for the clinical symptoms of CAIS in the patient. The levels of the AR transcript in peripheral blood leukocytes were higher in the patient than in her heterozygous mother and her heterozygous sister, as well as in the two healthy sisters. It is hypothesized that elevated levels of the AR transcript in the patient might be caused by the inability of the truncated receptor to react with IFI-16, which functions in complex with AR to inhibit the expression of the AR gene.
对一名具有女性表型、46,XY核型且诊断为完全雄激素不敏感综合征（CAIS）的患者进行了检查。她的母亲和三名46,XX姐妹也被纳入该研究。雄激素受体基因（AR）的序列分析显示存在一个新的A2933插入，该插入将酪氨酸密码子改变为终止密码子（Y857X），导致受体截短。计算机模拟显示容纳激素的疏水口袋发生了主要构象变化。insA2933导致截短的受体无法结合配体，并导致该患者出现CAIS的临床症状。患者外周血白细胞中AR转录本的水平高于其杂合子母亲和杂合子姐妹，以及两名健康姐妹。据推测，患者中AR转录本水平升高可能是由于截短的受体无法与IFI-16反应所致，IFI-16与AR形成复合物发挥作用以抑制AR基因的表达。
