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The second family affected with a PRDM8-related disease

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Abstract

Introduction

Lafora disease (LD) is a severe form of progressive myoclonus epilepsy characterized by generalized seizures, myoclonus, intellectual decline, ataxia, spasticity, dysarthria, visual loss, and in later stages, psychosis and dementia. To date, mutations in the EPM2A and EPM2B/NHLRC1 genes have been identified as the common causes of LD. However, a mutation in PRDM8 has been reported only once in a Pakistani family affected with early-onset Lafora disease. In the present study, we report the second family with a PRDM8 mutation.

Methods

Two affected individuals of an Iranian family initially diagnosed as complicated hereditary spastic paraplegia (HSP) underwent careful neurologic examination. Homozygosity mapping and whole-exome sequencing were performed. Based on the results of genetic analysis to detection of Lafora bodies, a skin biopsy was done.

Results

The clinical features of the patients were described. Linkage to chromosome 4 and a mutation in the PRDM8 gene were identified, suggesting the patients may be affected with early-onset LD. However, like the Pakistani family, the search for Lafora bodies in their skin biopsies was negative. Their electroencephalograms showed generalized epileptiform discharges in the absence of clinical seizures.

Conclusions

The current study increases the number of PRDM8-related cases and expands the phenotypic spectrum of mutations in the PRDM8 gene. Both reported PRDM8-related families presented intra and inter-familial heterogeneity and they have originated from the Middle East. Thus, it seems the PRDM8 mutations should be considered not only in LD but also in other neurodegenerative disorders such as a complicated HSP-like phenotype, especially in this region.

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Data availability

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

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Funding

Genetic Research Center, University of Social Welfare and Rehabilitation Sciences.

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Authors and Affiliations

  1. Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran

    Atefeh Davarzani, Seyyed Saleh Hashemi, Aida Ghasemi, Mohammad Reza Habibi Kavashkohei & Afagh Alavi

  2. Pediatric Neurorehabilitation Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran

    Amin Shahrokhi

  3. UCLA School of Public Health, 650 Charles E Young Dr S, Los Angeles, CA, 90095, USA

    Niloofar Farboodi

  4. The Edmond J. Safra Program in Parkinson’s Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital and Division of Neurology, University of Toronto, Toronto, ON, Canada

    Anthony E. Lang

  5. Krembil Brain Institute, Toronto, ON, Canada

    Anthony E. Lang

  6. Department of Dermatology, Rasoul Akram Hospital, School of Medicine, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Ghiasi

  7. Department of Neurology, Iran University of Medical Sciences, Tehran, Iran

    Mohammad Rohani

Authors
  1. Atefeh Davarzani
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  2. Amin Shahrokhi
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Correspondence to Mohammad Rohani or Afagh Alavi.

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All participants, after being informed of the nature of the research, consented to participate. This research was performed in accordance with the Declaration of Helsinki and with approval of the ethics board of the University of Social Welfare and Rehabilitation Sciences.

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Davarzani, A., Shahrokhi, A., Hashemi, S.S. et al. The second family affected with a PRDM8-related disease. Neurol Sci 43, 3847–3855 (2022). https://doi.org/10.1007/s10072-021-05815-w

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  • DOI: https://doi.org/10.1007/s10072-021-05815-w

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