dc.creatorMarino, Roxana Marcela
dc.creatorGarrido, Natalia Perez
dc.creatorCostanzo, Mariana
dc.creatorGuercio, Gabriela Viviana
dc.creatorJuanes, Matías Hernan
dc.creatorRocco, Carlos Alberto
dc.creatorRamirez, Pablo
dc.creatorWarman, Diana M.
dc.creatorCiaccio, Marta
dc.creatorPena, Gladys
dc.creatorFeyling, José García
dc.creatorMiras, Mirta Beatriz
dc.creatorRivarola, Marco Aurelio
dc.creatorBelgorosky, Alicia
dc.creatorSaraco, Nora Isabel
dc.date.accessioned2018-02-26T19:03:54Z
dc.date.available2018-02-26T19:03:54Z
dc.date.created2018-02-26T19:03:54Z
dc.date.issued2015-02
dc.identifierMarino, Roxana Marcela; Garrido, Natalia Perez; Costanzo, Mariana; Guercio, Gabriela Viviana; Juanes, Matías Hernan; et al.; Five new cases of 46, XX aromatase deficiency: Clinical follow-up from birth to puberty, a novel mutation, and a founder effect; Endocrine Society; Journal of Clinical Endocrinology and Metabolism; 100; 2; 2-2015; E301-E307
dc.identifier0021-972X
dc.identifierhttp://hdl.handle.net/11336/37138
dc.identifierCONICET Digital
dc.identifierCONICET
dc.description.abstractContext: Aromatase is the key enzyme for estrogen biosynthesis and is encoded by the CYP19A1 gene. Since 1991, several molecular CYP19A1 gene alterations associated with aromatase deficiency have been described in both sexes. Objective: The objective of the study was to detect CYP19A1 mutations in five aromatasedeficient 46, XX patients, to describe the clinical follow-up from birth to puberty and to perform haplotype analysis associated with the high-frequency c.628G>A splice mutation in Argentinean patients. Design: The design of the study was the sequencing of the coding and flanking intronic regions of the CYP19A1 gene in all patients and parents. Haplotype analysis of patients carrying the c.628G>A mutation was also performed. Patients: Clinical and biochemical findings in five new cases and one previously reported female aromatase-deficient patient (46, XX) are described. All patients presented with ambiguous genitalia at birth. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency as well as other steroidogenic defects were ruled out. Results: Phenotypic variability among the affected patients was found during follow-up. Direct sequencing of the CYP19A1 gene from genomic DNA revealed one novel mutation (c.574C>T) in two patients. In silico analysis predicted the c.574C>T mutation to be probably damaging. Four of six nonrelated patients presented with the c.628G>A splice mutation. Haplotype analysis showed that the c.628G>A splice mutation is associated with the same haplotype in our population. Conclusions: Increased knowledge on phenotypical variability found in female aromatase-deficient patients is useful to improve the detection rate in this disorder. In our population, a genetic founder defect has probably contributed to an increase in the incidence of the c.628G>A splice mutation.
dc.languageeng
dc.publisherEndocrine Society
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1210/jc.2014-2967
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jcem/article/100/2/E301/2814966
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectAromatase
dc.subjectAromatase Deficiency
dc.subjectFounder Effect
dc.titleFive new cases of 46, XX aromatase deficiency: Clinical follow-up from birth to puberty, a novel mutation, and a founder effect
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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