The Natural History of a Man With Ovotesticular 46,XX DSD Caused by a Novel 3-Mb 15q26.2 Deletion Containing NR2F2 Gene
| Autor: | Maria Isabel Melaragno, Mila Torii Corrêa Leite, Márcia Emília Francisco Shida, Magnus R. Dias-da-Silva, Ieda Therezinha do Nascimento Verreschi, Renata Ueta, Gianna Carvalheira, Patrícia Teófilo Monteagudo, Andréia Latanza Gomes Mathez, Andréa Cristina de Moraes Malinverni, Leonardo Cardili, Diego R. Mazzotti, Mariana Moysés-Oliveira, Miguel Angel Maluf |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Monosomy Endocrinology Diabetes and Metabolism Male sex determination 030209 endocrinology & metabolism Locus (genetics) Case Report Biology 46 XX DSD NR2F2 Gene 03 medical and health sciences 0302 clinical medicine Reproductive Biology and Sex-Based Medicine medicine Copy-number variation Gene Regulation of gene expression Genetics Ovotestis differences of sex development medicine.disease 030104 developmental biology copy-number variation transcription factor binding sites 15q26.2 deletion gene regulation |
| Zdroj: | Journal of the Endocrine Society |
| ISSN: | 2472-1972 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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