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Uniparental IsoDisomy: a case study on a new mechanism of Friedreich ataxia

European Journal of Human Genetics volume 33, pages 137–140 (2025)Cite this article

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Abstract

Friedreich’s Ataxia (FRDA) is the most common hereditary ataxia and is mainly caused by biallelic GAA repeat expansion in the FXN gene. Rare patients carrying FXN point mutations or intragenic deletions are reported. We describe the first FRDA patient with a chromosome 9 segmental Uniparental isoDisomy (UPiD) unmasking a homozygous FXN expansion initially undetected by TP-PCR. The child presented with a progressive proprioceptive ataxia associated with peripheral sensory neuronopathy and severe scoliosis. Whole genome sequencing (WGS) identified a maternal segmental Uniparental Isodisomy (UPiD) encompassing FXN. Short tandem repeats analysis on WGS showed a biallelic FXN expansion. The identification of a deletion in the primer-annealing region of the TP-PCR explained the initial TP-PCR failure. This is the first documented case of FRDA caused by segmental UPiD. This case highlights the complexity of the molecular diagnosis of FRDA, and emphasises the importance of integrating results from various technical diagnostic approaches.

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Fig. 1: Whole genome and FXN analysis in the patient and her parents.

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Data availability

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank the family for their participation in this study.

Funding

This manuscript did not receive any additional fund.

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Authors and Affiliations

  1. Service de Médecine Génomique des Maladies Rares, Hôpital Necker - Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France

    Brian Sperelakis-Beedham, Marine Rajaoba, Maryse Magen, Marie-Laure Maurin, Zahra Assouline, Julie Steffann & Giulia Barcia

  2. Imagine Institute, Genetics of Mitochondrial Disorders, INSERM, Paris, France

    Brian Sperelakis-Beedham, Zahra Assouline, Julie Steffann & Giulia Barcia

  3. Université Paris Cité, Paris, France

    Brian Sperelakis-Beedham, Cyril Gitiaux, Christine Barnerias, Isabelle Desguerre, Julie Steffann & Giulia Barcia

  4. Pediatric Neurology and Neurophysiology Department, Necker-Enfants-Malades Hospital, Assistance Publique-Hôpitaux, Paris, France

    Cyril Gitiaux, Christine Barnerias & Isabelle Desguerre

  5. Laboratoire de Biologie Médicale Multi-Sites SeqOIA Assistance-Publique, Paris, France

    Nicolas Derive, Jerome Chansard & Jean-Madeleine de Sainte Agathe

Authors
  1. Brian Sperelakis-Beedham
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  2. Cyril Gitiaux
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  4. Maryse Magen
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  7. Jean-Madeleine de Sainte Agathe
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  8. Marie-Laure Maurin
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  10. Christine Barnerias
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  11. Isabelle Desguerre
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  12. Julie Steffann
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  13. Giulia Barcia
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Contributions

Conceptualization: BSB, GB; Data curation: BSB, GB; Data analysis: BSB, MM, ND, JC, JMSA, MLM, ZA, JS, GB, Clinical data: CG, MR, CB, ID, GB; Writing original draft: BSB, GB; All authors read and approved the final manuscript.

Corresponding author

Correspondence to Giulia Barcia.

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Sperelakis-Beedham, B., Gitiaux, C., Rajaoba, M. et al. Uniparental IsoDisomy: a case study on a new mechanism of Friedreich ataxia. Eur J Hum Genet 33, 137–140 (2025). https://doi.org/10.1038/s41431-024-01728-2

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