Parental Origin of Gsα Mutations in the McCune-Albright Syndrome and in Isolated Endocrine Tumors

Giovanna Mantovani, Sara Bondioni, Andrea G. Lania, Sabrina Corbetta, Luisa de Sanctis, Marco Cappa, Eliana Di Battista, Philippe Chanson, Paolo Beck-Peccoz, Anna Spada
2004 Journal of Clinical Endocrinology and Metabolism  
Activating mutations of the G s ␣ gene are detected in different endocrine tumors, such as GH-secreting adenomas and toxic thyroid adenomas, and in hyperfunctioning glands from patients with McCune-Albright syndrome (MAS). There is increasing evidence that the G s ␣ gene is subjected to imprinting control and that G s ␣ imprinting plays a key role in the pathogenesis of different human diseases. The aim of this study was to investigate the presence of a parent specificity of G s ␣ mutations in
more » ... G s ␣ mutations in 10 patients affected with MAS and 12 isolated tumors (10 GH-secreting adenomas, one toxic thyroid adenoma, and one hyperfunctioning adrenal adenoma). The parental origin of G s ␣ mutations was assessed by evaluating NESP55 and exon 1A transcripts, which are monoallelically expressed from the maternal and paternal alleles, respectively. By this approach, we demonstrated that in isolated GH-secreting adenomas, as well as in MAS patients with acromegaly, G s ␣ mutations were on the maternal allele. By contrast, the involvement of other endocrine organs in MAS patients was not associated with a particular parent specificity, as precocious puberty and hyperthyroidism were present in patients with mutations on either the maternal or the paternal allele. Moreover, isolated hyperfunctioning thyroid and adrenal adenomas displayed the mutation on the maternal and paternal alleles, respectively. These data confirm the importance of G s ␣ imprinting in the pituitary gland and point out the high degree of tissue specificity of this phenomenon. (J Clin Endocrinol Metab 89: 3007-3009, 2004) DNA and RNA extractions and assay methods After obtaining written consent, DNA and RNA were extracted from the affected tissues (Table 2 ) using standard procedures (11, 17) . The G s ␣ gene (GenBank accession no.AH002748) was then amplified by PCR Abbreviation: MAS, McCune-Albright syndrome.
doi:10.1210/jc.2004-0194 pmid:15181091 fatcat:4jsd3xe6jrcjticecurupk6ozy