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A Novel Missense Variant in the Lmnb2 Gene Causes Progressive Myoclonus Epilepsy Publisher Pubmed



Soleimanipour F1 ; Razmara E2 ; Rahbarizadeh F1 ; Fallahi E3 ; Khodaeian M4 ; Tavasoli AR5 ; Garshasbi M2
Authors
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Authors Affiliations
  1. 1. Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  2. 2. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  3. 3. Department of Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran
  4. 4. Department of Medical Genetics, DeNA Laboratory, Tehran, Iran
  5. 5. Myelin Disorders Clinic, Pediatric Neurology Division, Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran

Source: Acta Neurologica Belgica Published:2022


Abstract

Progressive myoclonus epilepsies (PMEs) are a group of disorders embracing myoclonus, seizures, and neurological dysfunctions. Because of the genetic and clinical heterogeneity, a large proportion of PMEs cases have remained molecularly undiagnosed. The present study aimed to determine the underlying genetic factors that contribute to the PME phenotype in an Iranian female patient. We describe a consanguineous Iranian family with autosomal recessive PME that had remained undiagnosed despite extensive genetic and pathological tests. After performing neuroimaging and clinical examinations, due to heterogeneity of PMEs, the proband was subjected to paired-end whole-exome sequencing and the candidate variant was confirmed by Sanger sequencing. Various in-silico tools were also used to predict the pathogenicity of the variant. In this study, we identified a novel homozygous missense variant (NM_032737.4:c.472C > T; p.(Arg158Trp)) in the LMNB2 gene (OMIM: 150341) as the most likely disease-causing variant. Neuroimaging revealed a progressive significant generalized atrophy in the cerebral and cerebellum without significant white matter signal changes. Video-electroencephalography monitoring showed a generalized pattern of high-voltage sharp waves in addition to multifocal spikes and waves compatible with mixed type seizures and epileptic encephalopathic pattern. Herein, we introduce the second case of PME caused by a novel variant in the LMNB2 gene. This study also underscores the potentiality of next-generation sequencing in the genetic diagnosis of patients with neurologic diseases with an unknown cause. © 2021, Belgian Neurological Society.
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