Catch them if you are aware: PTEN postzygotic mosaicism in clinically suspicious patients with PTEN Hamartoma Tumour Syndrome and literature review |
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| Institution: | 1. Department of Human Genetics, Radboud university medical center, Nijmegen, the Netherlands;2. Radboud university medical center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands;3. Institute of Human Genetics, Medical Faculty, University of Bonn, Germany;4. Center for Hereditary Tumor Syndromes, University Hospital Bonn, Germany;5. Department of Pathology, Radboud university medical center, Nijmegen, the Netherlands;6. Radboud university medical center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands |
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| Abstract: | PTEN germline variants cause PTEN Hamartoma Tumour Syndrome (PHTS). Of individuals fulfilling diagnostic criteria, 41–88% test negative for PTEN germline variants, while mosaicism could be an explanation. Here we describe two individuals with PTEN mosaicism. First, a 21-year-old female presented with macrocephaly and a venous malformation. Next generation sequencing analysis on her venous malformation identified the mosaic pathogenic PTEN variant c.493-2A>G (23%). This variant was initially missed in blood due to low frequency (<1%), but detected in buccal swab (21%). Second, a 13-year-old male presented with macrocephaly, language developmental delay, behavioral problems, and an acral hyperkeratotic papule. Targeted PTEN analysis identified the mosaic pathogenic variant c.284C>T (11%) in blood, which was confirmed via buccal swab. These two cases suggest that PTEN mosaicism might be more common than currently reported. PTEN mosaicism awareness is important to enable diagnosis, which facilitates timely inclusion in cancer surveillance programs improving prognosis and life expectancy. |
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| Keywords: | Hamartoma syndrome Multiple Cowden syndrome Mosaicism |
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