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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorBATISTA, Rafael Loch
dc.contributor.authorYAMAGUCHI, Katsumi
dc.contributor.authorRODRIGUES, Andresa di Santi
dc.contributor.authorNISHI, Mirian Yumie
dc.contributor.authorGOODIER, John L.
dc.contributor.authorCARVALHO, Luciani Renata
dc.contributor.authorDOMENICE, Sorahia
dc.contributor.authorCOSTA, Elaine M. F.
dc.contributor.authorKAZAZIAN JR., Haig H.
dc.contributor.authorMENDONCA, Berenice Bilharinho
dc.identifier.citationJOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v.104, n.12, p.6385-6390, 2019
dc.description.abstractContext: 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). Objective: To identify the genetic etiology of AIS in a large multigenerational family with the PAIS phenotype. Participants: Nine affected individuals with clinical and laboratory findings consistent with PAIS and a normal exonic AR sequencing Settings: Endocrine clinic and genetic institute from two academic referral centers Design: Analysis of whole exons of the AR gene, including splicing regions, was performed, followed by sequencing of the 5'untranslated 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. Results: All 46,XY family members with PAIS had inherited, in hemizygosity, a complex defect (similar to 1100 bp) in the 5'UTR 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' UTR of the AR gene, severely reducing AR expression and leading to PAIS. Conclusion: 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.eng
dc.description.sponsorshipNational Institute of General Medical Studies, National Institutes of Health [303002/2016-6, 5R01GM099875-08]
dc.description.sponsorshipNational Institute on Aging, National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [1R21AG056840-01A1]
dc.publisherENDOCRINE SOCeng
dc.relation.ispartofJournal of Clinical Endocrinology & Metabolism
dc.titleMobile DNA in Endocrinology: LINE-1 Retrotransposon Causing Partial Androgen Insensitivity Syndromeeng
dc.rights.holderCopyright ENDOCRINE SOCeng
dc.subject.wosEndocrinology & Metabolismeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng, Katsumi:Johns Hopkins Univ Hosp, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA, John L.:Johns Hopkins Univ Hosp, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA JR., Haig H.:Johns Hopkins Univ Hosp, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA
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Appears in Collections:

Artigos e Materiais de Revistas Científicas - FM/MCM
Departamento de Clínica Médica - FM/MCM

Artigos e Materiais de Revistas Científicas - HC/ICESP
Instituto do Câncer do Estado de São Paulo - HC/ICESP

Artigos e Materiais de Revistas Científicas - HC/ICHC
Instituto Central - HC/ICHC

Artigos e Materiais de Revistas Científicas - HC/IPq
Instituto de Psiquiatria - HC/IPq

Artigos e Materiais de Revistas Científicas - LIM/42
LIM/42 - Laboratório de Hormônios e Genética Molecular

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