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Osteoporosis-pseudoglioma syndrome in four new patients: identification of two novel LRP5 variants and insights on patients’ management using bisphosphonates therapy

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Abstract

Summary

This study describes the clinical, radiological, and molecular data of four new patients with osteoporosis-pseudoglioma syndrome and assesses their response to bisphosphonate therapy.

Introduction

Osteoporosis-pseudoglioma syndrome (OPPG) is a very rare disorder characterized mainly by severe juvenile osteoporosis and congenital blindness. OPPG is caused by biallelic mutations in the gene encoding low-density lipoprotein receptor-related protein 5 (LRP5).

Methods

We present the clinical, radiological, and molecular findings of four new patients with OPPG from Egypt. We also assessed patients’ response to oral and intravenous bisphosphonate therapy.

Results

All patients had reduced bone mineral density (BMD) with variable number of fractures per year, in addition to bone abnormalities and the characteristic eye phenotype associated with OPPG. Mutation analyses of LRP5 gene revealed three different homozygous variants including two novel ones, c.7delG (p.A3Qfs*80) and c.3280G > A (p.E1094K). The c.3280G > A (p.E1094K) was recurrent in two unrelated patients who shared a unique haplotype suggesting a possible founder effect. The use of bisphosphonate therapy was beneficial; however, intravenous bisphosphonate administration led to a more favorable response.

Conclusion

Our study described the phenotypic and genetic features of four patients with OPPG and identified two new LRP5 variants, thus expanding the mutational spectrum of OPPG. In addition, our study reinforces the efficiency of using intravenous bisphosphonates in the management of patients with OPPG.

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Data availability

The data supporting the findings of this study are available with the corresponding author upon request.

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Acknowledgements

We thank all the patients and their family members who participated in our study.

Funding

This work was funded by a research grant from STDF (project no. 25877).

Author information

Authors and Affiliations

  1. Medical Molecular Genetics Department, Institute of Human Genetics and Genome Research, National Research Centre, Tahrir street, Dokki, Cairo, Egypt

    Mohamed S. Abdel-Hamid & Sherif F. Abdel-Ghafar

  2. Clinical Genetics Department, Institute of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt

    Rasha M. Elhossini, Ghada A. Otaify & Mona S. Aglan

Authors
  1. Mohamed S. Abdel-Hamid
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  2. Rasha M. Elhossini
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  3. Ghada A. Otaify
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  4. Sherif F. Abdel-Ghafar
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  5. Mona S. Aglan
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Corresponding author

Correspondence to Mohamed S. Abdel-Hamid.

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Ethics approval

This study was approved by the Medical Research Ethical Committee of the National Research Centre (NRC), Cairo, Egypt, and conducted in accordance with the declaration of Helsinki ethical principles for medical research involving human subjects. An informed consent was obtained from the patients and or their guardians.

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Abdel-Hamid, M.S., Elhossini, R.M., Otaify, G.A. et al. Osteoporosis-pseudoglioma syndrome in four new patients: identification of two novel LRP5 variants and insights on patients’ management using bisphosphonates therapy. Osteoporos Int 33, 1501–1510 (2022). https://doi.org/10.1007/s00198-022-06313-1

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  • DOI: https://doi.org/10.1007/s00198-022-06313-1

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