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We report here the case of a young patient without any remarkable familial medical history who was first referred at 7\u2009years of age, for an autism spectrum disorder (ASD) of Asperger type, not associated with macrocephaly. The patient subsequently presented at 10\u2009years 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 <jats:italic>PTEN<\/jats:italic> 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 <jats:italic>PTEN<\/jats:italic> variant. The anatomical distribution of the lesions suggests that the mutational event affecting <jats:italic>PTEN<\/jats:italic> occurred in neural crest progenitors, thus explaining the absence of macrocephaly. This report shows that mosaic alteration of <jats:italic>PTEN<\/jats:italic> 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.<\/jats:p>","DOI":"10.1186\/s40478-019-0841-0","type":"journal-article","created":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T13:02:57Z","timestamp":1575378177000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mosaic PTEN alteration in the neural crest during embryogenesis results in multiple nervous system hamartomas"],"prefix":"10.1186","volume":"7","author":[{"given":"Alice","family":"Goldenberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"Marguet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vianney","family":"Gilard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aude-Marie","family":"Cardine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnan","family":"Hassani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Doz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Radi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Vasseur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Bou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud","family":"Branchaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Houdayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Baert-Desurmont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Laquerriere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Frebourg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,3]]},"reference":[{"issue":"8","key":"841_CR1","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1038\/ng.3597","volume":"48","author":"JM Goldmann","year":"2016","unstructured":"Goldmann JM, Wong WS, Pinelli M, Farrah T, Bodian D, Stittrich AB et al (2016) Parent-of-origin-specific signatures of de novo mutations. 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