RGD Reference Report - Cushing's syndrome secondary to adrenocorticotropin-independent macronodular adrenocortical hyperplasia due to activating mutations of GNAS1 gene. - Rat Genome Database

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Cushing's syndrome secondary to adrenocorticotropin-independent macronodular adrenocortical hyperplasia due to activating mutations of GNAS1 gene.

Authors: Fragoso, MC  Domenice, S  Latronico, AC  Martin, RM  Pereira, MA  Zerbini, MC  Lucon, AM  Mendonca, BB 
Citation: Fragoso MC, etal., J Clin Endocrinol Metab. 2003 May;88(5):2147-51.
RGD ID: 11568052
Pubmed: (View Article at PubMed) PMID:12727968
DOI: Full-text: DOI:10.1210/jc.2002-021362

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is an uncommon cause of Cushing's syndrome characterized by bilateral nodular adrenocortical hyperfunction in the presence of suppressed ACTH levels. We investigated whether activating mutations in the ACTH receptor (MC2-R) or G(s alpha) (GNAS1) genes might be involved in AIMAH genesis. Five women with Cushing's syndrome due to AIMAH, confirmed by histological studies, and no signs of McCune-Albright syndrome were selected for molecular analysis of these genes. The single exon of the MC2-R gene and exons 8 and 9 of the GNAS1 gene were amplified by PCR in genomic DNA from adrenal nodules and peripheral blood. Direct sequencing revealed only MC2-R wild-type sequences. GNAS1 PCR products at denaturing gradient gel electrophoresis revealed abnormal migration patterns in adrenal tissues of three patients. Automatic sequencing showed two different activating mutations at codon Arg(201) of GNAS1, a substitution by histidine in two cases and by serine in one case. In conclusion, we found two different gsp mutations in three patients with Cushing's syndrome due to AIMAH, and we speculate whether they belong to the spectrum of McCune-Albright syndrome or whether these are the first reported cases of AIMAH due to gsp mutations.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Gnas  (GNAS complex locus)

Genes (Mus musculus)
Gnas  (GNAS (guanine nucleotide binding protein, alpha stimulating) complex locus)

Genes (Homo sapiens)
GNAS  (GNAS complex locus)


Additional Information