Congenital lipoid adrenal hyperplasia caused by a novel splicing mutation in the gene for the steroidogenic acute regulatory protein

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dc.contributor.authorGonzalez, AA
dc.contributor.authorReyes, ML
dc.contributor.authorCarvajal, CA
dc.contributor.authorTobar, JA
dc.contributor.authorMosso, LM
dc.contributor.authorBaquedano, P
dc.contributor.authorSolar, A
dc.contributor.authorVenegas, A
dc.contributor.authorFardella, CE
dc.date.accessioned2024-01-10T13:47:08Z
dc.date.available2024-01-10T13:47:08Z
dc.date.issued2004
dc.description.abstractSteroidogenic acute regulatory protein (StAR) plays a crucial role in the transport of cholesterol from the cytoplasm to the inner mitochondrial membrane, facilitating its conversion to pregnenolone by cytochrome P450scc. Its essential role in steroidogenesis was demonstrated after observing that StAR gene mutations gave rise to a potentially lethal disease named congenital lipoid adrenal hyperplasia, in which virtually no steroids are produced. We report here a 2-month-old female patient, karyotype 46XY, who presented with growth failure, convulsions, dehydration, hypoglycemia, hyponatremia, hypotension, and severe hyperpigmentation suggestive of adrenal insufficiency. Serum cortisol, 17OH-progesterone, dehydroepiandrosterone sulfate, testosterone, 17OH-pregnenolone, and aldosterone levels were undetectable in the presence of high ACTH and plasma renin activity levels. Immunohistochemical analysis of testis tissues revealed the absence of StAR protein. Molecular analysis of StAR gene demonstrated a homozygous G to T mutation within the splice donor site of exon 1 (IVS1 + 1G>T). Her parents and one brother were heterozygous for this mutation. In vitro analysis of the mutation was performed in COS cells transfected with minigenes coding regions spanning exon-intron 1 to 3 carrying the mutant and the wild-type sequences. RT-PCR analyses of the mutant gene showed an abnormal mRNA transcript of 2430 bp (normal size 433 bp). Sequence analysis of the mutant mRNA demonstrated the retention of intron 1. Immunolocalization of the StAR minigene product detected the peptide in the mitochondria of COS cells transfected with the wild-type minigene but not in those transfected with the mutant minigene. We conclude that this mutation gives rise to a truncated StAR protein, which lacks an important N-terminal region and the entire lipid transfer domain.
dc.fechaingreso.objetodigital2024-05-15
dc.format.extent6 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1210/jc.2003-030345
dc.identifier.issn0021-972X
dc.identifier.pubmedidMEDLINE:14764819
dc.identifier.urihttps://doi.org/10.1210/jc.2003-030345
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/79239
dc.identifier.wosidWOS:000188763900075
dc.information.autorucMedicina;Carvajal C;S/I;8586
dc.information.autorucMedicina;Fardella C;S/I;66235
dc.information.autorucMedicina;Mosso L;S/I;88201
dc.issue.numero2
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final951
dc.pagina.inicio946
dc.publisherENDOCRINE SOC
dc.revistaJOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
dc.rightsacceso restringido
dc.subjectSTAR GENE
dc.subjectMITOCHONDRIAL PROTEIN
dc.subjectCHOLESTEROL
dc.subjectEXPRESSION
dc.subjectIMPORT
dc.subjectCELLS
dc.subjectSITE
dc.subject.ods03 Good Health and Well-being
dc.subject.ods05 Gender Equality
dc.subject.odspa03 Salud y bienestar
dc.subject.odspa05 Igualdad de género
dc.titleCongenital lipoid adrenal hyperplasia caused by a novel splicing mutation in the gene for the steroidogenic acute regulatory protein
dc.typeartículo
dc.volumen89
sipa.codpersvinculados8586
sipa.codpersvinculados66235
sipa.codpersvinculados88201
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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