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Mosaicism in PTEN—new case and comment on the literature

European Journal of Human Genetics volume 30, pages 641–644 (2022)Cite this article

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PTEN hamartoma tumor syndrome (PHTS) encompasses a group of related genetic disorders linked to inherited pathogenic variants (PVs) in PTEN gene, which includes Cowden syndrome (CS), Bannayan–Riley–Ruvalcaba syndrome (BRRS), Lhermitte–Duclos Disease (LDD) in adults, autism disorders associated with macrocephaly, PTEN-related Proteus syndrome (PS) and Proteus-like syndrome [1, 2]. Accumulated evidence suggests that these entities represent variable expression and age-related penetrance of one single condition [2]. CS is a rare autosomal dominant condition with an incidence of ~1:200,000 individuals [2], characterized by a varied spectrum of clinical manifestations, even among patients carrying the same variant. Some of the most common phenotypic features include the development of hamartomatous polyps in the gastrointestinal tract, reported in 35–85% of CS patients, macrocephaly and mucocutaneous lesions as trichilemmomas. Besides, CS patients present increased risks for breast, endometrial and thyroid tumors [1, 2]. The operational diagnosis of CS is based upon the phenotypic manifestations [1] or the identification of a PTEN PV, which may be inherited or arise de novo in up to 44% of patients [2]. Interestingly, PTEN mosaicism has been reported in 3 patients with a clinical diagnosis of CS, as well as in 3 additional patients with PHTS-associated features z(Table 1).

Table 1 Summary of previously published PTEN mosaicisms and their clinical and genetic features.
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Fig. 1: Cowden syndrome patient and mutational analysis of PTEN c.331T>C pathogenic variant.

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All the data generated in this study can be found within the published article and its Supplementary files.

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Acknowledgements

We thank CERCA Program/Generalitat de Catalunya for their institutional support. We also wish to thank all the members of the ICO Hereditary Cancer Program.

Funding

Supported by the Carlos III National Health Institute and Ministerio de Ciencia e Innovación, funded by FEDER funds—a way to build Europe—[PI19/00553; PI16/00563; PID2019-111254RB-I00] and CIBERONC [CB16/12/00234]; the Government of Catalonia [Pla estratègic de recerca i innovació en salut (PERIS_MedPerCan and URDCat projects), 2017SGR1282 and 2017SGR496].

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Author notes

  1. These authors jointly supervised this work: Jesús del Valle, Conxi Lázaro.

Authors and Affiliations

  1. Hereditary Cancer Program, Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), IDIBELL, Catalan Institute of Oncology, l’Hospitalet del Llobregat, Spain

    Paula Rofes, Álex Teulé, Lídia Feliubadaló, Mònica Salinas, Raquel Cuesta, Sílvia Iglesias, Olga Campos, Sara González, Gabriel Capellá, Joan Brunet, Jesús del Valle & Conxi Lázaro

  2. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain

    Paula Rofes, Lídia Feliubadaló, Sara González, Gabriel Capellá, Joan Brunet, Jesús del Valle & Conxi Lázaro

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Contributions

PR, JV, and CL conceived, designed, and planned the study; PR, LF, RC, OC, SG, GC, JV, and CL contributed to the acquisition, analysis, and/or interpretation of the molecular data; AT, MS, SI, and JB provided samples and clinical data; PR, AT, and CL drafted the manuscript. All authors critically reviewed the manuscript for intellectual content and approved the final version.

Corresponding author

Correspondence to Conxi Lázaro.

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Competing interests

The authors declare no competing interests.

Ethical approval

Informed written consent for both diagnostic and research purposes was obtained from the patient presented here. The study protocol was approved by the ethics committee of Bellvitge Biomedical Research Institute (IDIBELL; PR278/19).

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Rofes, P., Teulé, Á., Feliubadaló, L. et al. Mosaicism in PTEN—new case and comment on the literature. Eur J Hum Genet 30, 641–644 (2022). https://doi.org/10.1038/s41431-022-01052-7

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