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

Autor:	Carvalheira G; Department of Morphology and Genetics, Division of Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Malinverni AM; Department of Morphology and Genetics, Division of Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.; Department of Pathology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Moysés-Oliveira M; Department of Morphology and Genetics, Division of Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Ueta R; Department of Morphology and Genetics, Division of Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Cardili L; Department of Pathology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Monteagudo P; Department of Medicine, Division of Endocrinology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Mathez ALG; Department of Medicine, Division of Endocrinology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Verreschi IT; Department of Medicine, Division of Endocrinology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Maluf MA; Department of Medicine, Division of Cardiovascular, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Shida MEF; Department of Medicine, Division of Pediatric Surgery, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Leite MTC; Department of Medicine, Division of Pediatric Surgery, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Mazzotti D; Center for Sleep and Circadian Neurobiology, University of Pensylvania, Philadelphia, Pennsylvania., Melaragno MI; Department of Morphology and Genetics, Division of Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., Dias-da-Silva MR; Department of Medicine, Division of Endocrinology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.; Department of Medicine, Division of Endocrinology, Laboratory of Molecular and Translational Endocrinology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Journal of the Endocrine Society [J Endocr Soc] 2019 Aug 28; Vol. 3 (11), pp. 2107-2113. Date of Electronic Publication: 2019 Aug 28 (Print Publication: 2019).
DOI:	10.1210/js.2019-00241
Abstrakt:	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 © 2019 Endocrine Society.)
Databáze:	MEDLINE
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