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A novel missense variant in the LMNB2 gene causes progressive myoclonus epilepsy

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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.

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Data availability

Human variant and phenotypes have been reported to ClinVar (Accession number: SCV001448673; https://www.ncbi.nlm.nih.gov/clinvar/SCV001448673) and LOVD (individual ID: 00324284; https://databases.lovd.nl/shared/individuals/00324284).

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Acknowledgements

We are grateful to the family for their willing participation and cooperation with us and also are thankful to the staff of DeNA Laboratory, Tehran, Iran, for their assistance.

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The authors did not receive support from any organization for the submitted work.

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Authors and Affiliations

  1. Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Fardin Soleimanipour & Fatemeh Rahbarizadeh

  2. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Ehsan Razmara & Masoud Garshasbi

  3. Department of Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran

    Elnaz Fallahi

  4. Department of Medical Genetics, DeNA Laboratory, Tehran, Iran

    Mehrnoosh Khodaeian

  5. Myelin Disorders Clinic, Pediatric Neurology Division, Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran

    Ali Reza Tavasoli

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  1. Fardin Soleimanipour
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  4. Elnaz Fallahi
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  7. Masoud Garshasbi
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Contributions

Conceived and designed the experiments: MG, MKH, and FS. Conducted the experiments: MKH and FS. Analyzed and interpreted the data: ER, FR, EF, and ART. Contributed reagents/materials/analysis tools: MG and FS. Wrote the paper: ER. Depicted the figures: ER. Funding acquisition: MG. Project administration: MG. All authors read and approved the final manuscript.

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Correspondence to Masoud Garshasbi.

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This study was approved by the ethics committee of Tarbiat Modares University, Tehran, Iran and has, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Soleimanipour, F., Razmara, E., Rahbarizadeh, F. et al. A novel missense variant in the LMNB2 gene causes progressive myoclonus epilepsy. Acta Neurol Belg 122, 659–667 (2022). https://doi.org/10.1007/s13760-021-01650-0

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