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2p25.3 microduplications involving MYT1L: further phenotypic characterization through an assessment of 16 new cases and a literature review

European Journal of Human Genetics volume 31, pages 895–904 (2023)Cite this article

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Abstract

Microduplications involving the MYT1L gene have mostly been described in series of patients with isolated schizophrenia. However, few reports have been published, and the phenotype has still not been well characterized. We sought to further characterize the phenotypic spectrum of this condition by describing the clinical features of patients with a pure 2p25.3 microduplication that includes all or part of MYT1L. We assessed 16 new patients with pure 2p25.3 microduplications recruited through a French national collaboration (n = 15) and the DECIPHER database (n = 1). We also reviewed 27 patients reported in the literature. For each case, we recorded clinical data, the microduplication size, and the inheritance pattern. The clinical features were variable and included developmental and speech delays (33%), autism spectrum disorder (ASD, 23%), mild-to-moderate intellectual disability (ID, 21%), schizophrenia (23%), or behavioral disorders (16%). Eleven patients did not have an obvious neuropsychiatric disorder. The microduplications ranged from 62.4 kb to 3.8 Mb in size and led to duplication of all or part of MYT1L; seven of these duplications were intragenic. The inheritance pattern was available for 18 patients: the microduplication was inherited in 13 cases, and all parents but one had normal phenotype. Our comprehensive review and expansion of the phenotypic spectrum associated with 2p25.3 microduplications involving MYT1L should help clinicians to better assess, counsel and manage affected individuals. MYT1L microduplications are characterized by a spectrum of neuropsychiatric phenotypes with incomplete penetrance and variable expressivity, which are probably due to as-yet unknown genetic and nongenetic modifiers.

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Fig. 1: Mapping of the 2p25.3 duplications in the cohort, including new cases (N1-N15), patients described in the literature (P1-P27), and the new case recruited through the DECIPHER database (D1).

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Data availability

The datasets generated for the current study are included in this article, further inquiries can be directed to the corresponding authors. The variants reported in patients N1–N5 and described in this study have been submitted to the ClinVar repository (SUB12521627, accession numbers SCV002818537-SCV002818541). All the other newly reported variants have been submitted to the DECIPHER database.

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Acknowledgements

We thank the patients and their families for their cooperation. This study assessed data generated by the DECIPHER community. A full list of the centers that helped to generate the data is available from https://deciphergenomics.org/about/stats and by e-mail from contact@deciphergenomics.org. Funding for the DECIPHER project was provided by the Wellcome Trust. We declare that those who carried out the original analysis and collection of the data bear no responsibility for the further analysis or interpretation of the data.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Département de Génétique, Laboratoire de Biologie Médicale, CHI de Poissy-St Germain en Laye, F-78300, Poissy, France

    Malek Bouassida, Rodolphe Dard, Juliette Clorennec, François Vialard & Bérénice Hervé

  2. Service de Génétique, Centre Hospitalier Universitaire de Poitiers, F-86021, Poitiers, France

    Matthieu Egloff & Gwenaël Le Guyader

  3. Département de Génétique, Hôpital Robert Debré, APHP, F-75019, Paris, France

    Jonathan Levy & Anne-Claude Tabet

  4. Service de cytogénétique, Groupement Hospitalier Est, Hospices Civils de Lyon, F-69500, Bron, France

    Nicolas Chatron & Caroline Schluth-Bolard

  5. Istituto CSS-Mendel, It-00198, Roma, Italy

    Laura Bernardini & Maria Grazia Giuffrida

  6. Department of Life, Health and Environmental Sciences, University of L’Aquila Piazzale Salvatore Tommasi, It-67100, Coppito - L’Aquila, Italy

    Francesco Brancati

  7. San Raffaele Roma, IRCCS, It-00163, Roma, Italy

    Francesco Brancati

  8. RHuMA Team, UMR-BREED, INRA-UVSQ-ENVA, UFR Simone Veil Santé, F-78380, Montigny-le-Bretonneux, France

    Rodolphe Dard, Juliette Clorennec & François Vialard

  9. Department of Genetics and Reference Center for Developmental Disorders, Normandie Univ, UNIROUEN, Inserm U1245 and CHU Rouen, F-76000, Rouen, France

    Juliette Coursimault

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  1. Malek Bouassida
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Contributions

MB, FV and BH: contributed to the study conception and design. MB: analyzed the data and wrote the manuscript. JL, GL, FB, MGG, RD: performed the clinical evaluation of the patients. ME, NC, LB, ACT, CSB, JCo: performed the genetic investigations. JCl: participated in the collection of clinical data. FV, BH: did the supervision, review and editing of the manuscript. All authors contributed to data acquisition.

Corresponding authors

Correspondence to Malek Bouassida or François Vialard.

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In compliance with the Declaration of Helsinki, informed written consent for genetic study was obtained for participated individuals.

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The authors declare no competing interests.

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Bouassida, M., Egloff, M., Levy, J. et al. 2p25.3 microduplications involving MYT1L: further phenotypic characterization through an assessment of 16 new cases and a literature review. Eur J Hum Genet 31, 895–904 (2023). https://doi.org/10.1038/s41431-023-01379-9

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