Chromatin conformation capture in the clinic: 4C-seq/HiC distinguishes pathogenic from neutral duplications at the GPR101 locus

[Background]: X-linked acrogigantism (X-LAG; MIM: 300942) is a severe form of pituitary gigantism caused by chromosome Xq26.3 duplications involving GPR101. X-LAG-associated duplications disrupt the integrity of the topologically associating domain (TAD) containing GPR101 and lead to the formation o...

Descripción completa

Detalles Bibliográficos
Autores: Daly, Adrian F., Dunnington, Leslie A., Rodriguez-Buritica, David F., Spiegel, Erica, Brancati, Francesco, Mantovani, Giovanna, Rawal, Vandana M., Rueda Faucz, Fabio, Hijazi, Hadia, Caberg, Jean-Hubert, Nardone, Anna Maria, Bengala, Mario, Fortugno, Paola, Sindaco, Giulia Del, Ragonese, Marta, Gould, Helen, Cannavò, Salvatore, Petrossians, Patrick, Lania, Andrea G., Lupski, James R., Beckers, Albert, Stratakis, Constantine A., Levy, Brynn, Trivellin, Giampaolo, Franke, Martin
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/372314
Acceso en línea:http://hdl.handle.net/10261/372314
Access Level:acceso abierto
Palabra clave:GPR101
Topologically associating domains
Neo-TAD
X-linked acrogigantism
Pituitary tumor
Prenatal diagnosis
Chromosome microarray
4C
HiC
Enhancer
Descripción
Sumario:[Background]: X-linked acrogigantism (X-LAG; MIM: 300942) is a severe form of pituitary gigantism caused by chromosome Xq26.3 duplications involving GPR101. X-LAG-associated duplications disrupt the integrity of the topologically associating domain (TAD) containing GPR101 and lead to the formation of a neo-TAD that drives pituitary GPR101 misexpression and gigantism. As X-LAG is fully penetrant and heritable, duplications involving GPR101 identified on prenatal screening studies, like amniocentesis, can pose an interpretation challenge for medical geneticists and raise important concerns for patients and families. Therefore, providing robust information on the functional genomic impact of such duplications has important research and clinical value with respect to gene regulation and triplosensitivity traits.

Similares en LA Referencia