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dc.contributor.author
Baquedano, María Sonia  
dc.contributor.author
Guercio, Gabriela Viviana  
dc.contributor.author
Marino, Roxana Marcela  
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Berensztein, Esperanza Beatriz  
dc.contributor.author
Costanzo, Mariana  
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Bailez, Marcela  
dc.contributor.author
Vaiani, Elisa  
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Maceiras, Mercedes Carmen  
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Ramirez, Pablo  
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Chaler, Eduardo Adrian  
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Rivarola, Marco Aurelio  
dc.contributor.author
Belgorosky, Alicia  
dc.date.available
2023-04-18T12:49:44Z  
dc.date.issued
2011-12  
dc.identifier.citation
Baquedano, María Sonia; Guercio, Gabriela Viviana; Marino, Roxana Marcela; Berensztein, Esperanza Beatriz; Costanzo, Mariana; et al.; Unique dominant negative mutation in the N-terminal mitochondrial targeting sequence of StAR, causing a variant form of congenital lipoid adrenal hyperplasia; Endocrine Society; Journal of Clinical Endocrinology and Metabolism; 98; 1; 12-2011; 1945-7197  
dc.identifier.issn
0021-972X  
dc.identifier.uri
http://hdl.handle.net/11336/194323  
dc.description.abstract
Context: Steroid acute regulatory (StAR) protein is a mitochondria-targeted protein that is part of the transduceosome complex crucial for transport of cholesterol to mitochondria. Recessive mutations cause classic and nonclassic congenital lipoid adrenal hyperplasia. Objective: The aim of this study was to report the clinical, hormonal, genetic, and functional data of a novel heterozygous mutation in the StAR gene found in a 46,XY patient with ambiguous genitalia and neonatal severe steroidogenic deficiency. Patient: Undetectable serum steroids with high ACTH and plasma renin activity but normal acute GnRH response were found in infancy. After gonadectomy (at 3 yr of age), serum LH and testosterone were undetectable, whereas FSH was normal but increased slowly afterward. Estrogen replacement therapy, started at 10.2 yr of age, suppressed gonadotropins (for 2 yr). However, after 1 month off estrogens, the patient showed castrated levels. At 11.9 yr old, after fludrocortisone withdrawal because of hypertension, plasma renin activity and aldosterone remained normal, suggesting mineralocorticoid recovery by a StAR-independent mechanism. Results: We found a de novo heterozygous IVS-2A>G StAR mutation and the reported heterozygous p.G146A SF1 polymorphism with normal CYP11A1, FDXR, FDX1, VDAC1, and TSPO genes. The mutant StAR transcript lacked exon 2, resulting in the in-frame loss of amino acids 22 to 59 in the N-terminal mitochondrial targeting signal. In vitro, the mutant protein exhibited reduced StAR activity in a dominant-negative manner and almost no mitochondria localization. Conclusions: A misfolded p.G22-L59del StAR might interfere with wild-type StAR activity by blocking the transduceosome complex, causing an autosomal dominant form of StAR deficiency, explaining the clinical phenotype. We speculated that estrogen might have modulated mineralocorticoid function and pubertal maturation in a human natural model lacking endogenous steroid production.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Endocrine Society  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
StAR  
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MITOCHONDRIAL  
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LIPOID  
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HYPERPLASIA  
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Endocrinología y Metabolismo  
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Medicina Clínica  
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CIENCIAS MÉDICAS Y DE LA SALUD  
dc.title
Unique dominant negative mutation in the N-terminal mitochondrial targeting sequence of StAR, causing a variant form of congenital lipoid adrenal hyperplasia  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2023-04-17T13:49:43Z  
dc.journal.volume
98  
dc.journal.number
1  
dc.journal.pagination
1945-7197  
dc.journal.pais
Estados Unidos  
dc.description.fil
Fil: Baquedano, María Sonia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina  
dc.description.fil
Fil: Guercio, Gabriela Viviana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina  
dc.description.fil
Fil: Marino, Roxana Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina  
dc.description.fil
Fil: Berensztein, Esperanza Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina  
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Fil: Costanzo, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina  
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Fil: Bailez, Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina  
dc.description.fil
Fil: Vaiani, Elisa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina  
dc.description.fil
Fil: Maceiras, Mercedes Carmen. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina  
dc.description.fil
Fil: Ramirez, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina  
dc.description.fil
Fil: Chaler, Eduardo Adrian. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina  
dc.description.fil
Fil: Rivarola, Marco Aurelio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina  
dc.description.fil
Fil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina  
dc.journal.title
Journal of Clinical Endocrinology and Metabolism  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1210/jc.2012-2865