BROX haploinsufficiency in familial nonmedullary thyroid cancer
| Autor: | Domenico Salvatore, Daniela Esposito, Furio Pacini, Silvia Cantara, P. Sabatino, Annalaura Torella, F. Del Vecchio Blanco, Vincenzo Nigro, Giacomo Accardo, Maria Grazia Castagna, Daniela Pasquali, Filomena Barbato |
|---|---|
| Přispěvatelé: | Pasquali, D., Torella, A., Accardo, G., Esposito, D., Del Vecchio Blanco, F., Salvatore, D., Sabatino, P., Pacini, F., Barbato, F., Castagna, M. G., Cantara, S., Nigro, V. |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine EGFR Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Haploinsufficiency Biology Thyroid cancer Papillary thyroid cancer Frameshift mutation 03 medical and health sciences symbols.namesake 0302 clinical medicine Endocrinology medicine Humans Genetic Predisposition to Disease Genetic Testing Thyroid Neoplasms Gene Germ-Line Mutation Genetic testing Thyroid Genetics HABP2 Endosomal Sorting Complexes Required for Transport medicine.diagnostic_test FNMTC Middle Aged Prognosis medicine.disease Penetrance 030104 developmental biology BROX Thyroid Cancer Papillary NGS Mendelian inheritance symbols Female |
| Zdroj: | Journal of Endocrinological Investigation. 44:165-171 |
| ISSN: | 1720-8386 |
| DOI: | 10.1007/s40618-020-01286-6 |
| Popis: | Background: The familial nonmedullary thyroid cancer (FNMTC) is suspected to be a Mendelian condition in up to 3–8% of thyroid cancers. The susceptibility chromosomal loci and genes of 95% of FNMTC cases remain to be characterized. The inheritance of FNMTC appears to be autosomal dominant with incomplete penetrance and variable expressivity. The finding of the causative gene of FNMTC and the identification of patients at risk that need genetic testing were our aim. Methods: We analyzed by whole-exome sequencing patients and non-affected relatives of five families with at least two family members affected by papillary thyroid cancer, selecting for new or extremely rare variants with predicted pathogenic value. Results: A family showed, in all three affected members, a new loss-of-function variant (frameshift deletion) in BROX gene at 1q41 that was absent from all internal and external databases. In a second family with three affected relatives, we found an additional new BROX variant. The smaller families presented no variants in BROX or in the other causative genes studied. Conclusions: BROX could be a new causative gene for FNMTC. Variants in BROX may result in the haploinsufficiency of a key gene involved in the morphogenesis of MVBs, in the endosomal sorting of cargo proteins, and in EGFR. Functional studies are needed to support this result. The thorough genomic analysis by NGS in all families with three or more affected members should become a routine approach to obtain a comprehensive genetic view and find confirmative second cases. |
| Databáze: | OpenAIRE |
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