Screening for Mutations in the Steroidogenic Acute Regulatory Protein and Steroidogenic Factor-1 Genes, and in CYP11A and Dosage-Sensitive Sex Reversal-Adrenal Hypoplasia Gene on the X Chromosome, Gene-1 (DAX-1), in Hyperandrogenic Hirsute Women1

C change in exon 6, resulting in an Arg(365)Pro mutation, was found in 1 of 45 patients, but not in controls. Also, a Gly(146)Ala missense mutation, resulting from a G-->C change in exon 4, was found in 2 of 48 patients and in 2 of 50 nonaffected individuals. We identified a C-->T base pair change at position -33 of the StAR gene. Three of 48 patients and 3 of 43 controls presented this variant. No mutations were found in coding regions of the StAR gene. Analysis of CYP11A-coding regions identified a G-->A change in exon 3, resulting in a Val(179)Ile missense mutation. This mutation was found in 1 of 29 patients studied and was not present in 50 controls. Finally, analysis of DAX-1 showed no variant in any of the women studied. In conclusion, mutations in StAR, SF-1, CYP11A, and DAX-1 are seldom found in hirsute patients and do not explain the steroidogenic abnormalities found in these women.
This work was supported by grants from the Consejerı´a de Investigacio ´n y Cultura, Comunidad de Madrid, Spain (Proyecto 08.6/0022/ 1998 to H.F.E.-M.), and from the Fondo de Investigacio´n Sanitaria, Ministerio de Sanidad y Consumo, Spain (Proyecto FIS 00/0414 to H.F.E.-M., and Contrato FIS 98/3044 to R.M.C.). -->
Popis souboru: 154852 bytes; application/pdf
ISSN: 1945-7197
0021-972X
DOI: 10.1210/jcem.86.4.7424
Přístupová URL adresa: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::17017afe069165924d19cdd3b8a13a83
https://doi.org/10.1210/jcem.86.4.7424
Rights: OPEN
Přírůstkové číslo: edsair.doi.dedup.....17017afe069165924d19cdd3b8a13a83
Autor: Miryam Asunción, José L. San Millán, Rosa M. Calvo, José Sancho, D Telleria, Héctor F. Escobar-Morreale
Rok vydání: 2001
Předmět:
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
ISSN: 1945-7197
0021-972X
DOI: 10.1210/jcem.86.4.7424
Popis: 4 pages, 1 table.-- Presented in part at the 82nd Annual Meeting of The Endocrine Society, Toronto, Ontario, Canada, June 21–24, 2000.
Abnormalities in adrenal and/or ovarian steroidogenesis are found in most patients with hirsutism. The rate-limiting step in the synthesis of steroids in the ovary and the adrenal is the conversion of cholesterol into pregnenolone by cholesterol side-chain cleavage enzyme (P450scc), encoded by the gene CYP11A, after cholesterol is introduced into the mitochondria by the steroidogenic acute regulatory protein (StAR). DAX-1 is a repressor of StAR gene expression, and steroidogenic factor-1 (SF-1) is a regulator of CYP11A, DAX-1, and StAR gene. Mutations in any of these factors resulting in gain of function, or loss of repression, of StAR or P450scc might contribute to the steroidogenic abnormalities present in hirsute patients. In the present study we have screened, using heteroduplex analysis, the genes encoding StAR and SF-1 as well as DAX-1 and CYP11A for mutations in genomic DNA from 19 women presenting with hirsutism and increased serum androgen levels. When variants were found, analysis was extended to a larger group of hyperandrogenic patients and nonaffected women. Two variants were identified in the SF-1 gene. A G-->C change in exon 6, resulting in an Arg(365)Pro mutation, was found in 1 of 45 patients, but not in controls. Also, a Gly(146)Ala missense mutation, resulting from a G-->C change in exon 4, was found in 2 of 48 patients and in 2 of 50 nonaffected individuals. We identified a C-->T base pair change at position -33 of the StAR gene. Three of 48 patients and 3 of 43 controls presented this variant. No mutations were found in coding regions of the StAR gene. Analysis of CYP11A-coding regions identified a G-->A change in exon 3, resulting in a Val(179)Ile missense mutation. This mutation was found in 1 of 29 patients studied and was not present in 50 controls. Finally, analysis of DAX-1 showed no variant in any of the women studied. In conclusion, mutations in StAR, SF-1, CYP11A, and DAX-1 are seldom found in hirsute patients and do not explain the steroidogenic abnormalities found in these women.
This work was supported by grants from the Consejerı´a de Investigacio ´n y Cultura, Comunidad de Madrid, Spain (Proyecto 08.6/0022/ 1998 to H.F.E.-M.), and from the Fondo de Investigacio´n Sanitaria, Ministerio de Sanidad y Consumo, Spain (Proyecto FIS 00/0414 to H.F.E.-M., and Contrato FIS 98/3044 to R.M.C.).
Databáze: OpenAIRE
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