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Novel PXDN biallelic variants in patients with microphthalmia and anterior segment dysgenesis

Journal of Human Genetics volume 65, pages 487–491 (2020)Cite this article

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Abstract

Microphthalmia, anophthalmia, and anterior segment dysgenesis are severe ocular developmental defects. There is a wide genetic heterogeneity leading to these ocular malformations. By using whole genome, exome and targeted sequencing in patients with ocular developmental anomalies, six biallelic pathogenic variants (including five novel variants) were identified in the PXDN gene in four families with microphthalmia and anterior segment dysgenesis. Only 11 different mutations (11 families) have been described in this gene to date. The phenotype of these patients is variable in severity, ranging from cataract and developmental glaucoma to complex microphthalmia. Interestingly, two unrelated patients of our series presented with an ocular phenotype including aniridia and microspherophakia. However, despite various phenotypic presentations and types of mutations, no genotype-phenotype correlation could be made. Thus, this work improves our knowledge of the recessive phenotype associated with biallelic variants in this gene and highlights the importance of screening PXDN in patients with anterior segment dysgenesis with or without microphthalmia.

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Acknowledgements

This work was supported by grants from the Instituto de Salud Carlos III n67 CIBERER (06/07/0036), FIS (PI17/01164), and Miguel Servet Program (CPII17_00006), the European Regional Development Funds, the Regional Government of Madrid (CAM, B2017/BMD37) from the Spanish Foundation of Rare Diseases (FEDER), and from the French Fondation Maladies Rares. We acknowledge Bianca Millon-Devigne for her help.

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Author notes

  1. Nicolas Chassaing

    Present address: Génétique Médicale, Hôpital Purpan, 31300, Toulouse, France

  2. These authors contributed equally: Celia Zazo Seco, Julie Plaisancié

Authors and Affiliations

  1. UDEAR, UMR 1056 Inserm-Université de Toulouse, Toulouse, France

    Celia Zazo-Seco, Julie Plaisancié, Patrick Calvas & Nicolas Chassaing

  2. Department of Medical Genetics, CHU Toulouse, Toulouse, France

    Julie Plaisancié, Patrick Calvas & Nicolas Chassaing

  3. SIDVA 91, Ophthalmic Genetics, Juvisy-sur-Orge, France

    Pierre Bitoun

  4. Department of Genetics, Fundación Jiménez Díaz University Hospital, CIBERER, (IIS-FJD, UAM), Madrid, Spain

    Marta Corton, Ana Arteche & Carmen Ayuso

  5. Division of Medical Genetics, Einstein Healthcare Network, Philadelphia, PA, USA

    Adele Schneider

  6. Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands

    Dimitra Zafeiropoulou & Christian Gilissen

  7. Department of Ophthalmology, IHU Necker-Enfants-Malades, Paris-Descartes University, Paris, France

    Olivier Roche

  8. Department of Ophthalmology, CHU Toulouse, Toulouse, France

    Felix Frémont

  9. Department of Pediatrics, University of California, San Francisco, CA, USA

    Anne Slavotinek

  10. Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK

    Nicola Ragge

  11. West Midlands Regional Genetics Service and Birmingham Health Partners Birmingham Women’s and Children’s Hospital NHS Foundation Trust, Birmingham, UK

    Nicola Ragge

Authors
  1. Celia Zazo-Seco
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  2. Julie Plaisancié
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  6. Carmen Ayuso
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  8. Dimitra Zafeiropoulou
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  9. Christian Gilissen
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  10. Olivier Roche
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  11. Felix Frémont
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  12. Patrick Calvas
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  13. Anne Slavotinek
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  14. Nicola Ragge
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  15. Nicolas Chassaing
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Correspondence to Nicolas Chassaing.

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Zazo-Seco, C., Plaisancié, J., Bitoun, P. et al. Novel PXDN biallelic variants in patients with microphthalmia and anterior segment dysgenesis. J Hum Genet 65, 487–491 (2020). https://doi.org/10.1038/s10038-020-0726-x

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  • DOI: https://doi.org/10.1038/s10038-020-0726-x

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