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Mosaic PTEN alteration in the neural crest during embryogenesis results in multiple nervous system hamartomas
The contribution of mosaic alterations to tumors of the nervous system and to non-malignant neurological diseases has been unmasked thanks to the development of Next Generation Sequencing (NGS) technologies. We report here the case of a young patient without any remarkable familial medical history w...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892231/ https://www.ncbi.nlm.nih.gov/pubmed/31796102 http://dx.doi.org/10.1186/s40478-019-0841-0 |
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author | Goldenberg, Alice Marguet, Florent Gilard, Vianney Cardine, Aude-Marie Hassani, Adnan Doz, François Radi, Sophie Vasseur, Stéphanie Bou, Jacqueline Branchaud, Maud Houdayer, Claude Baert-Desurmont, Stéphanie Laquerriere, Annie Frebourg, Thierry |
author_facet | Goldenberg, Alice Marguet, Florent Gilard, Vianney Cardine, Aude-Marie Hassani, Adnan Doz, François Radi, Sophie Vasseur, Stéphanie Bou, Jacqueline Branchaud, Maud Houdayer, Claude Baert-Desurmont, Stéphanie Laquerriere, Annie Frebourg, Thierry |
author_sort | Goldenberg, Alice |
collection | PubMed |
description | The contribution of mosaic alterations to tumors of the nervous system and to non-malignant neurological diseases has been unmasked thanks to the development of Next Generation Sequencing (NGS) technologies. We report here the case of a young patient without any remarkable familial medical history who was first referred at 7 years of age, for an autism spectrum disorder (ASD) of Asperger type, not associated with macrocephaly. The patient subsequently presented at 10 years of age with multiple nodular lesions located within the trigeminal, facial and acoustic nerve ganglia and at the L3 level. Histological examination of this latter lesion revealed a glioneuronal hamartoma, exhibiting heterogeneous PTEN immunoreactivity, astrocyte and endothelial cell nuclei expressing PTEN, but not ganglion cells. NGS performed on the hamartoma allowed the detection of a PTEN pathogenic variant in 30% of the reads. The presence of this variant in the DNA extracted from blood and buccal swabs in 3.5 and 11% of the NGS reads, respectively, confirmed the mosaic state of the PTEN variant. The anatomical distribution of the lesions suggests that the mutational event affecting PTEN occurred in neural crest progenitors, thus explaining the absence of macrocephaly. This report shows that mosaic alteration of PTEN may result in multiple central and peripheral nervous system hamartomas and that the presence of such alteration should be considered in patients with multiple nervous system masses, even in the absence of cardinal features of PTEN hamartoma tumor syndrome, especially macrocephaly. |
format | Online Article Text |
id | pubmed-6892231 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-68922312019-12-11 Mosaic PTEN alteration in the neural crest during embryogenesis results in multiple nervous system hamartomas Goldenberg, Alice Marguet, Florent Gilard, Vianney Cardine, Aude-Marie Hassani, Adnan Doz, François Radi, Sophie Vasseur, Stéphanie Bou, Jacqueline Branchaud, Maud Houdayer, Claude Baert-Desurmont, Stéphanie Laquerriere, Annie Frebourg, Thierry Acta Neuropathol Commun Case Report The contribution of mosaic alterations to tumors of the nervous system and to non-malignant neurological diseases has been unmasked thanks to the development of Next Generation Sequencing (NGS) technologies. We report here the case of a young patient without any remarkable familial medical history who was first referred at 7 years of age, for an autism spectrum disorder (ASD) of Asperger type, not associated with macrocephaly. The patient subsequently presented at 10 years of age with multiple nodular lesions located within the trigeminal, facial and acoustic nerve ganglia and at the L3 level. Histological examination of this latter lesion revealed a glioneuronal hamartoma, exhibiting heterogeneous PTEN immunoreactivity, astrocyte and endothelial cell nuclei expressing PTEN, but not ganglion cells. NGS performed on the hamartoma allowed the detection of a PTEN pathogenic variant in 30% of the reads. The presence of this variant in the DNA extracted from blood and buccal swabs in 3.5 and 11% of the NGS reads, respectively, confirmed the mosaic state of the PTEN variant. The anatomical distribution of the lesions suggests that the mutational event affecting PTEN occurred in neural crest progenitors, thus explaining the absence of macrocephaly. This report shows that mosaic alteration of PTEN may result in multiple central and peripheral nervous system hamartomas and that the presence of such alteration should be considered in patients with multiple nervous system masses, even in the absence of cardinal features of PTEN hamartoma tumor syndrome, especially macrocephaly. BioMed Central 2019-12-03 /pmc/articles/PMC6892231/ /pubmed/31796102 http://dx.doi.org/10.1186/s40478-019-0841-0 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Case Report Goldenberg, Alice Marguet, Florent Gilard, Vianney Cardine, Aude-Marie Hassani, Adnan Doz, François Radi, Sophie Vasseur, Stéphanie Bou, Jacqueline Branchaud, Maud Houdayer, Claude Baert-Desurmont, Stéphanie Laquerriere, Annie Frebourg, Thierry Mosaic PTEN alteration in the neural crest during embryogenesis results in multiple nervous system hamartomas |
title | Mosaic PTEN alteration in the neural crest during embryogenesis results in multiple nervous system hamartomas |
title_full | Mosaic PTEN alteration in the neural crest during embryogenesis results in multiple nervous system hamartomas |
title_fullStr | Mosaic PTEN alteration in the neural crest during embryogenesis results in multiple nervous system hamartomas |
title_full_unstemmed | Mosaic PTEN alteration in the neural crest during embryogenesis results in multiple nervous system hamartomas |
title_short | Mosaic PTEN alteration in the neural crest during embryogenesis results in multiple nervous system hamartomas |
title_sort | mosaic pten alteration in the neural crest during embryogenesis results in multiple nervous system hamartomas |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892231/ https://www.ncbi.nlm.nih.gov/pubmed/31796102 http://dx.doi.org/10.1186/s40478-019-0841-0 |
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