{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:40:06Z","timestamp":1790779206113,"version":"4.1.0"},"reference-count":15,"publisher":"The Endocrine Society","issue":"12","funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cientfico e Tecnolgico","doi-asserted-by":"publisher","award":["303002\/2016-6"],"award-info":[{"award-number":["303002\/2016-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["5R01GM099875-08"],"award-info":[{"award-number":["5R01GM099875-08"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["1R21AG056840-01A1"],"award-info":[{"award-number":["1R21AG056840-01A1"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Androgen insensitivity syndrome (AIS) is the most common cause of disorders of sex development in 46,XY individuals. It is an X-linked condition usually caused by pathogenic allelic variants in the androgen receptor (AR) gene. The phenotype depends on the AR variant, ranging from severe undervirilization (complete AIS) to several degrees of external genitalia undervirilization. Although 90% of those with complete AIS will have AR mutations, this will only be true for 40% of those with partial AIS (PAIS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To identify the genetic etiology of AIS in a large multigenerational family with the PAIS phenotype.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>Nine affected individuals with clinical and laboratory findings consistent with PAIS and a normal exonic AR sequencing<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Settings<\/jats:title>\n                  <jats:p>Endocrine clinic and genetic institute from two academic referral centers<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Analysis of whole exons of the AR gene, including splicing regions, was performed, followed by sequencing of the 5\u2032untranslated region (UTR) of the AR gene. Detailed phenotyping was performed at the initial diagnosis and long-term follow-up, and circulating levels of steroid gonadal hormones were measured in all affected individuals. AR expression was measured using RT-PCR and cultured fibroblasts.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>All 46,XY family members with PAIS had inherited, in hemizygosity, a complex defect (\u223c1100 bp) in the 5\u2032UTR region of the AR surrounded by a duplicated 18-bp sequence (target site duplication). This sequence is 99.7% similar to an active, long, interspersed element present on the X chromosome (AC002980; Xq22.2), which was inserted in the 5\u2032UTR of the AR gene, severely reducing AR expression and leading to PAIS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The molecular diagnosis of PAIS remains challenging. The genomic effect of retrotransposon mobilization should be considered a possible molecular cause of AIS and other AR diseases.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2019-00144","type":"journal-article","created":{"date-parts":[[2019,8,8]],"date-time":"2019-08-08T09:04:57Z","timestamp":1565255097000},"page":"6385-6390","source":"Crossref","is-referenced-by-count":17,"title":["Mobile DNA in Endocrinology: LINE-1 Retrotransposon Causing Partial Androgen Insensitivity Syndrome"],"prefix":"10.1210","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5461-0301","authenticated-orcid":false,"given":"Rafael Loch","family":"Batista","sequence":"first","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular, da Disciplina de Endocrinologia e Metabologia do Hospital das Cl\u00ednicas da Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"},{"name":"McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins Hospital, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsumi","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins Hospital, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andresa di Santi","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular, da Disciplina de Endocrinologia e Metabologia do Hospital das Cl\u00ednicas da Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirian Yumie","family":"Nishi","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular, da Disciplina de Endocrinologia e Metabologia do Hospital das Cl\u00ednicas da Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L","family":"Goodier","sequence":"additional","affiliation":[{"name":"McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins Hospital, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciani Renata","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular, da Disciplina de Endocrinologia e Metabologia do Hospital das Cl\u00ednicas da Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorahia","family":"Domenice","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do 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