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The Second Family Affected With a Prdm8-Related Disease Publisher Pubmed



Davarzani A1 ; Shahrokhi A2 ; Hashemi SS1 ; Ghasemi A1 ; Habibi Kavashkohei MR1 ; Farboodi N3 ; Lang AE4, 5 ; Ghiasi M6 ; Rohani M7 ; Alavi A1
Authors
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Authors Affiliations
  1. 1. Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
  2. 2. Pediatric Neurorehabilitation Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
  3. 3. UCLA School of Public Health, 650 Charles E Young Dr S, Los Angeles, 90095, CA, United States
  4. 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
  5. 5. Krembil Brain Institute, Toronto, ON, Canada
  6. 6. Department of Dermatology, Rasoul Akram Hospital, School of Medicine, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Neurology, Iran University of Medical Sciences, Tehran, Iran

Source: Neurological Sciences Published:2022


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. © 2021, Fondazione Societa Italiana di Neurologia.