2026-05-17T01:18:28Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/260112025-12-18T12:56:34Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991

00925njm 22002777a 4500 dc Mellid, Sara author Coloma, Javier author Calsina, Bruna author Monteagudo, María author Roldán-Romero, Juan M author Santos, María author Leandro-García, Luis J author Lanillos, Javier author Martínez-Montes, Ángel M author Rodríguez-Antona, Cristina author Montero-Conde, Cristina author Martínez-López, Joaquín author Ayala, Rosa author Matias-Guiu, Xavier author Robledo Batanero, Mercedes author Cascón, Alberto author 2020-11-09 Over the past few years, next generation technologies have been applied to unravel the genetics of rare inherited diseases, facilitating the discovery of new susceptibility genes. We recently found germline gain-of-function variants in two patients with head and neck paragangliomas causing a characteristic hypermethylated DNA profile. Here, whole-exome sequencing identifies a novel germline variant (p.Gly332Arg) in a patient with bilateral carotid paragangliomas, papillary thyroid carcinoma and idiopathic intellectual disability. The variant, located in the Pro-Trp-Trp-Pro (PWWP) domain of the protein involved in chromatin targeting, affects a residue mutated in papillary thyroid tumors and located between the two residues found mutated in microcephalic dwarfism patients. Structural modelling of the variant in the DNMT3A PWWP domain predicts that the interaction with H3K36me3 will be altered. An increased methylation of target genes, compatible with a gain-of-function effect of the alteration, was observed in saliva DNA from the proband and in one independent acute myeloid leukemia sample carrying the same p.Gly332Arg variant. Although further studies are needed to support a causal role of variants in paraganglioma, the description of a new alteration in a patient with multiple clinical features suggests a heterogeneous phenotypic spectrum related to germline variants. Cancers (Basel) . 2020 Nov 9;12(11):3304 Cancers (BASEL) 33182397 https://hdl.handle.net/20.500.12105/26011 DNMT3A germline variant papillary thyroid carcinoma paraganglioma Novel Germline Variant in a Patient with Multiple Paragangliomas and Papillary Thyroid Carcinoma.