The Natural History of a Man With Ovotesticular 46,XX DSD Caused by a Novel 3-Mb 15q26.2 Deletion Containing NR2F2 Gene

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Carvalheira, Gianna ^[1] ; Malinverni, Andrea M. ^{[1, 2]} ; Moyses-Oliveira, Mariana ^[1] ; Ueta, Renata ^[1] ; Cardili, Leonardo ^[2] ; Monteagudo, Patricia ^[3] ; Mathez, Andreia L. G. ^[3] ; Verreschi, Ieda T. ^[3] ; Maluf, Miguel A. ^[4] ; Shida, Marcia E. F. ^[5] ; Leite, Mila T. C. ^[5] ; Mazzotti, Diego ^[6] ; Melaragno, Maria Isabel ^[1] ; Dias-da-Silva, Magnus R. ^{[3, 7]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo UNIFESP, Dept Morphol & Genet, Div Genet, Escola Paulista Med, BR-04023900 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo UNIFESP, Dept Pathol, Escola Paulista Med, BR-04023900 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo UNIFESP, Dept Med, Div Endocrinol, Escola Paulista Med, BR-04023900 Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo UNIFESP, Dept Med, Div Cardiovasc, Escola Paulista Med, BR-04023900 Sao Paulo - Brazil

^[5] Univ Fed Sao Paulo UNIFESP, Dept Med, Div Pediat Surg, Escola Paulista Med, BR-04023900 Sao Paulo - Brazil

^[6] Univ Pensylvania, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 - USA

^[7] Univ Fed Sao Paulo UNIFESP, Dept Med, Div Endocrinol, Lab Mol & Translat Endocrinol, Escola Paulista Med, BR-04023900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF THE ENDOCRINE SOCIETY; v. 3, n. 11, p. 2107-2113, NOV 2019.
• Citações Web of Science: 0

Resumo

Gonadal sex determination is a complex genetic process by which an embryonic primordium is driven to form an ovary or a testis, which requires a delicate dosage balance involving many genes. Disruption in this molecular pathway can lead to differences of sex development (DSD). Although some genetic mechanisms leading to 46,XY DSD have been elucidated, little is known about copy-number variation (CNV) causing testicular or ovotesticular 46,XX DSD. We describe a 20-year natural history of a man with SRY-negative 46,XX who was born with atypical male external genitalia, aortic coarctation, and bilateral blepharophimosis-ptosis. The molecular study identified a de novo heterozygous 3-Mb 15q26.2 deletion, a gene-poor locus containing NR2F2, which encodes the nuclear receptor COUP-TFII that is highly expressed in ovary and cardiac arteries. Immunohistochemistry confirmed the low COUP-TFII expression on his ovotestis tissue. Monosomy of 15q26.2, encompassing the NR2F2 gene, may act as a Z-factor regulating the male sex determination negatively. This finding supports a novel type of CNV resulting in DSD in an individual who developed male puberty spontaneously. Copyright (C) 2019 Endocrine Society (AU)

• Processo FAPESP: 14/11572-8 - Rearranjos cromossômicos e sua importância na etiologia das doenças genéticas: investigação citogenômica e molecular
• Beneficiário: Maria Isabel de Souza Aranha Melaragno
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/20747-8 - Investigação clínica, bioquímica e molecular da paralisia periódica tirotóxica
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