Constantine A. Stratakis1,2, María A. Tichomirowa3, Sosipatros A. Boikos2, Matheus Azevedo2, Maya Lodish1,2, Marco Martari4, Santosh Kumar Verma1,2, AF Daly3, Margarita Raygada2, MF Keil1,2, J. Papademetriou2, Limor Drori-Herishanu2, Anélia Horvath2, K.M. Tsang2, Maria Nesterova2, Samantha Franklin5, Jean-François Vanbellinghen6, Vincent Bours6, Roberto Salvatori4, Albert Beckers3
1Pediatric Endocrinology Inter-Institute Training Program (PEITP), Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institute of Health (NIH), Bethesda, MD 20892, USA
2Section on Endocrinology Genetics, Program on Developmental Endocrinology Genetics (PDEGEN)
3Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, 4000 Liège, Belgium
4Division of Endocrinology, Johns Hopkins University, Baltimore, MD 21287, USA
5Pediatric Endocrinology, San Diego, CA 92123, USA
6Department of Medical Genetics, Centre Hospitalier Universitaire de Liège, University of Liège, 4000 Liège, Belgium
Tóm tắt
Stratakis CA, Tichomirowa MA, Boikos S, Azevedo MF, Lodish M, Martari M, Verma S, Daly AF, Raygada M, Keil MF, Papademetriou J, Drori‐Herishanu L, Horvath A, Tsang KM, Nesterova M, Franklin S, Vanbellinghen J‐F, Bours V, Salvatori R, Beckers A. The role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes.The prevalence of germline mutations in MEN1, AIP, PRKAR1A, CDKN1B and CDKN2CI is unknown among pediatric patients with pituitary adenomas (PA). In this study, we screened children with PA for mutations in these genes; somatic GNAS mutations were also studied in a limited number of growth hormone (GH) or prolactin (PRL)‐secreting PA. We studied 74 and 6 patients with either isolated Cushing disease (CD) or GH‐ or PRL‐secreting PA, respectively. We also screened four pediatric patients with CD, and four with GH/PRL‐secreting tumors who had some syndromic features. There was one AIP mutation (p.Lys103Arg) among 74 CD patients. Two MEN1 mutations that occurred in patients with recurrent or difficult‐to‐treat disease were found among patients with CD. There was one MEN1 and three AIP mutations (p.Gln307ProfsX104, p.Pro114fsX, p.Lys241X) among pediatric patients with isolated GH‐ or PRL‐secreting PA and one additional MEN1 mutation in a patient with positive family history. There were no mutations in the PRKAR1A, CDKN1B, CDKN2C or GNAS genes. Thus, germline AIP or MEN1 gene mutations are frequent among pediatric patients with GH‐ or PRL‐secreting PA but are significantly rarer in pediatric CD; PRKAR1A mutations are not present in PA outside of Carney complex.
