G2Cdb::Human Disease report

Disease id
D00000148
Name
Cushing's syndrome
Nervous system disease
no

Genes (1)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00001473 GNAS
GNAS complex locus
Y (12727968) Microinsertion (MI) Y

References

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

    Fragoso MC, Domenice S, Latronico AC, Martin RM, Pereira MA, Zerbini MC, Lucon AM and Mendonca BB

    Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM-42, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil 01060-970. mariofragoso@uol.com.br

    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.

    The Journal of clinical endocrinology and metabolism 2003;88;5;2147-51

Literature (1)

Pubmed - human_disease

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

    Fragoso MC, Domenice S, Latronico AC, Martin RM, Pereira MA, Zerbini MC, Lucon AM and Mendonca BB

    Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM-42, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil 01060-970. mariofragoso@uol.com.br

    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.

    The Journal of clinical endocrinology and metabolism 2003;88;5;2147-51

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

Cookies Policy | Terms and Conditions. This site is hosted by Edinburgh University and the Genes to Cognition Programme.