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Population screening for 15q11-q13 duplications: corroboration of the difference in impact between maternally and paternally inherited alleles

European Journal of Human Genetics volume 32, pages 31–36 (2024)Cite this article

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Abstract

Maternally inherited 15q11-q13 duplications are generally found to cause more severe neurodevelopmental anomalies compared to paternally inherited duplications. However, this assessment is mainly inferred from the study of patient populations, causing an ascertainment bias towards patients at the more severe end of the phenotypic spectrum. Here, we analyze the low coverage genome-wide cell-free DNA sequencing data obtained from pregnant women during non-invasive prenatal screening (NIPS). We detect 23 15q11-q13 duplications in 333,187 pregnant women (0.0069%), with an approximately equal distribution between maternal and paternal duplications. Maternally inherited duplications are always associated with a clinical phenotype (ranging from learning difficulties to intellectual impairment, epilepsy and psychiatric disorders), while paternal duplications are normal or associated with milder phenotypes (mild learning difficulties and dyslexia). This data corroborates the difference in impact between paternally and maternally inherited 15q11-q13 duplications, contributing to the improvement of genetic counselling. We recommend reporting 15q11-q13 duplications identified during genome-wide NIPS with appropriate genetic counselling for these pregnant women in the interest of both mothers and future children.

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Fig. 1: Genomic representation of the 15q11-q13 region.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request and within ethical constraints.

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Acknowledgements

We would like to thank all participating women, clinicians and laboratory staff. We also thank the Genomics Core (KU Leuven) for their sequencing and bioinformatic support.

Funding

Funding for this study is provided by the KU Leuven (C14/22/125) and the FWO-SBO-MICADO S003422.

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Authors and Affiliations

  1. Center for Human Genetics, University Hospitals Leuven–KU Leuven, Leuven, Belgium

    Ilse Parijs, Nathalie Brison, Leen Vancoillie, Koenraad Devriendt, Kris Van Den Bogaert & Joris Robert Vermeesch

  2. Center of Medical Genetics, University Hospital Ghent, Ghent, Belgium

    Machteld Baetens, Sandra Janssens & Björn Menten

  3. Center of Medical Genetics, University and University Hospital Antwerp, Antwerp, Belgium

    Bettina Blaumeiser & Katrien Janssens

  4. Center for Medical Genetics, Institut de Pathologie et de Génétique Gosselies, Charleroi, Belgium

    Sébastien Boulanger, Julie Désir, Axel Marichal & Colombine Meunier

  5. Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Clinical Sciences, research group Reproduction and Genetics, Center for Medical Genetics, Brussels, Belgium

    Boyan Dimitrov, Nathalie Fieremans, Kim Van Berkel & Ann Van Den Bogaert

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  1. Ilse Parijs
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Contributions

Conceptualization: IP, KVDB, KD, JRV. Investigation and methodology: IP, KVDB, KD, JRV. Formal analysis: IP. Visualization: IP. Data curation: IP, NB, LV, KJ, BB, MB, SJ, BM, BD, NF, KVB, AVDB, CM, JD, SB, AM. Supervision: KVDB, KD, JRV. Writing—original draft, review, and editing: IP, KJ, MB, BM, NF, KVDB, KJ, KD, JRV.

Corresponding author

Correspondence to Joris Robert Vermeesch.

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The authors declare no competing interests.

Ethical approval

This study is approved by the Ethics Committee Research of University Hospitals Leuven (S66428).

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Parijs, I., Brison, N., Vancoillie, L. et al. Population screening for 15q11-q13 duplications: corroboration of the difference in impact between maternally and paternally inherited alleles. Eur J Hum Genet 32, 31–36 (2024). https://doi.org/10.1038/s41431-023-01336-6

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