Considerations on diagnosis and surveillance measures of PTEN hamartoma tumor syndrome: clinical and genetic study in a series of Spanish patients
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Published:2022-02-28
Issue:1
Volume:17
Page:
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ISSN:1750-1172
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Container-title:Orphanet Journal of Rare Diseases
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language:en
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Short-container-title:Orphanet J Rare Dis
Author:
Pena-Couso Laura, Ercibengoa María, Mercadillo Fátima, Gómez-Sánchez David, Inglada-Pérez Lucía, Santos María, Lanillos Javier, Gutiérrez-Abad David, Hernández Almudena, Carbonell Pablo, Letón Rocío, Robledo Mercedes, Rodríguez-Antona Cristina, Perea José, Urioste MiguelORCID, Alonso Miguel Ángel, Andrés Raquel, Arévalo Sara, del Mar Arias María, Balmaña Judith, Beristain Elena, Blanco Ignacio, Boronat Mauro, Brunet Joan, Cózar María Victoria, del Campo Miguel, Díaz Arantza, Gabau Elisabeth, Barcina María Jesús, González Margarita, Guitart Miriam, Hernán Imma, Hernández Héctor Salvador, Hernando Susana, Lacambra Carmen, Lasa Adriana, Lastra Enrique, Llort Gemma, del Rosario Marín María, Marrupe David, Martínez Francisco, Martínez Víctor, Martorell Loreto, Orera María, Pedrinaci Susana, Pérez Pedro, Pineda Marta, Plasencia Ana María, Cajal Teresa Ramón y, Robles Luis, Rodà Diana, Rodríguez Nuria, Rosell Jordi, Sáez Raquel, Salvat Mónica, Sánchez Antonio, Santana Alfredo, Soto José Luis, Toll Agustín, Tuneu Anna, Vázquez Carlos,
Abstract
Abstract
Background
The limited knowledge about the PTEN hamartoma tumor syndrome (PHTS) makes its diagnosis a challenging task. We aimed to define the clinical and genetic characteristics of this syndrome in the Spanish population and to identify new genes potentially associated with the disease.
Results
We reviewed the clinical data collected through a specific questionnaire in a series of 145 Spanish patients with a phenotypic features compatible with PHTS and performed molecular characterization through several approaches including next generation sequencing and whole exome sequencing (WES). Macrocephaly, mucocutaneous lesions, gastrointestinal polyposis and obesity are prevalent phenotypic features in PHTS and help predict the presence of a PTEN germline variant in our population. We also find that PHTS patients are at risk to develop cancer in childhood or adolescence. Furthermore, we observe a high frequency of variants in exon 1 of PTEN, which are associated with renal cancer and overexpression of KLLN and PTEN. Moreover, WES revealed variants in genes like NEDD4 that merit further research.
Conclusions
This study expands previously reported findings in other PHTS population studies and makes new contributions regarding clinical and molecular aspects of PHTS, which are useful for translation to the clinic and for new research lines.
Funder
instituto de salud carlos iii
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Genetics (clinical),General Medicine
Reference39 articles.
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