Whole-exome identifies RXRG and TH germline variants in familial isolated prolactinoma
| Autor: | Eitan Friedman, Tom Curran, Luiz De Marco, Patrícia P. Couto, Eduardo P. Dias, Raony G.C. Lisboa, Flávia M. Melo, Flávia Maria Lopes Passos, Allen E. Bale, Jessica M.Y. Ng, Luciana Bastos-Rodrigues |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Adenoma
Adult Male 0301 basic medicine Cancer Research Tyrosine 3-Monooxygenase Receptors Prolactin DNA Mutational Analysis 030209 endocrinology & metabolism Biology Germline 03 medical and health sciences symbols.namesake 0302 clinical medicine Germline mutation Proto-Oncogene Proteins Genotype Genetics medicine Humans Retinoid X Receptor gamma Computer Simulation Exome Genetic Predisposition to Disease Prolactinoma MEN1 Molecular Biology Gene Germ-Line Mutation Sanger sequencing Intracellular Signaling Peptides and Proteins Genetic disorder medicine.disease Pedigree 030104 developmental biology symbols Female Growth Hormone-Secreting Pituitary Adenoma |
| Zdroj: | Cancer Genetics. 209:251-257 |
| ISSN: | 2210-7762 |
| DOI: | 10.1016/j.cancergen.2016.05.065 |
| Popis: | Familial isolated pituitary adenoma (FIPA) is a rare genetic disorder. In a subset of FIPA families AIP germline mutations have been reported, but in most FIPA cases the exact genetic defect remains unknown. The present study aimed to determine the genetic basis of FIPA in a Brazilian family. Three siblings presented with isolated prolactin genes. Further mutation screening was performed using whole-exome sequencing and all likely causative mutations were validated by Sanger sequencing. In silico analysis and secreting pituitary adenoma diagnosed through clinical, biochemical and imaging testing. Sanger sequencing was used to genotype candidate prolactinoma-mutated additional predictive algorithms were applied to prioritize likely pathogenic variants. No mutations in the coding and flanking intronic regions in the MEN1, AIP and PRLR genes were detected. Whole-exome sequencing of three affected siblings revealed novel, predicted damaging, heterozygous variants in three different genes: RXRG, REXO4 and TH. In conclusion, the RXRG and TH possibly pathogenic variants may be associated with isolated prolactinoma in the studied family. The possible contribution of these genes to additional FIPA families should be explored. |
| Databáze: | OpenAIRE |
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