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Novel Genetic and Phenotypic Expansion in GOSR2-Related Progressive Myoclonus Epilepsy

Biallelic variants in the Golgi SNAP receptor complex member 2 gene (GOSR2) have been reported in progressive myoclonus epilepsy with neurodegeneration. Typical clinical features include ataxia and areflexia during early childhood, followed by seizures, scoliosis, dysarthria, and myoclonus. Here, we...

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Autores principales: Hentrich, Lea, Parnes, Mered, Lotze, Timothy Edward, Coorg, Rohini, de Koning, Tom J., Nguyen, Kha M., Yip, Calvin K., Jungbluth, Heinz, Koy, Anne, Dafsari, Hormos Salimi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606070/
https://www.ncbi.nlm.nih.gov/pubmed/37895210
http://dx.doi.org/10.3390/genes14101860
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author Hentrich, Lea
Parnes, Mered
Lotze, Timothy Edward
Coorg, Rohini
de Koning, Tom J.
Nguyen, Kha M.
Yip, Calvin K.
Jungbluth, Heinz
Koy, Anne
Dafsari, Hormos Salimi
author_facet Hentrich, Lea
Parnes, Mered
Lotze, Timothy Edward
Coorg, Rohini
de Koning, Tom J.
Nguyen, Kha M.
Yip, Calvin K.
Jungbluth, Heinz
Koy, Anne
Dafsari, Hormos Salimi
author_sort Hentrich, Lea
collection PubMed
description Biallelic variants in the Golgi SNAP receptor complex member 2 gene (GOSR2) have been reported in progressive myoclonus epilepsy with neurodegeneration. Typical clinical features include ataxia and areflexia during early childhood, followed by seizures, scoliosis, dysarthria, and myoclonus. Here, we report two novel patients from unrelated families with a GOSR2-related disorder and novel genetic and clinical findings. The first patient, a male compound heterozygous for the GOSR2 splice site variant c.336+1G>A and the novel c.364G>A,p.Glu122Lys missense variant showed global developmental delay and seizures at the age of 2 years, followed by myoclonus at the age of 8 years with partial response to clonazepam. The second patient, a female homozygous for the GOSR2 founder variant p.Gly144Trp, showed only mild fine motor developmental delay and generalized tonic–clonic seizures triggered by infections during adolescence, with seizure remission on levetiracetam. The associated movement disorder progressed atypically slowly during adolescence compared to its usual speed, from initial intention tremor and myoclonus to ataxia, hyporeflexia, dysmetria, and dystonia. These findings expand the genotype–phenotype spectrum of GOSR2-related disorders and suggest that GOSR2 should be included in the consideration of monogenetic causes of dystonia, global developmental delay, and seizures.
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spelling pubmed-106060702023-10-28 Novel Genetic and Phenotypic Expansion in GOSR2-Related Progressive Myoclonus Epilepsy Hentrich, Lea Parnes, Mered Lotze, Timothy Edward Coorg, Rohini de Koning, Tom J. Nguyen, Kha M. Yip, Calvin K. Jungbluth, Heinz Koy, Anne Dafsari, Hormos Salimi Genes (Basel) Article Biallelic variants in the Golgi SNAP receptor complex member 2 gene (GOSR2) have been reported in progressive myoclonus epilepsy with neurodegeneration. Typical clinical features include ataxia and areflexia during early childhood, followed by seizures, scoliosis, dysarthria, and myoclonus. Here, we report two novel patients from unrelated families with a GOSR2-related disorder and novel genetic and clinical findings. The first patient, a male compound heterozygous for the GOSR2 splice site variant c.336+1G>A and the novel c.364G>A,p.Glu122Lys missense variant showed global developmental delay and seizures at the age of 2 years, followed by myoclonus at the age of 8 years with partial response to clonazepam. The second patient, a female homozygous for the GOSR2 founder variant p.Gly144Trp, showed only mild fine motor developmental delay and generalized tonic–clonic seizures triggered by infections during adolescence, with seizure remission on levetiracetam. The associated movement disorder progressed atypically slowly during adolescence compared to its usual speed, from initial intention tremor and myoclonus to ataxia, hyporeflexia, dysmetria, and dystonia. These findings expand the genotype–phenotype spectrum of GOSR2-related disorders and suggest that GOSR2 should be included in the consideration of monogenetic causes of dystonia, global developmental delay, and seizures. MDPI 2023-09-25 /pmc/articles/PMC10606070/ /pubmed/37895210 http://dx.doi.org/10.3390/genes14101860 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hentrich, Lea
Parnes, Mered
Lotze, Timothy Edward
Coorg, Rohini
de Koning, Tom J.
Nguyen, Kha M.
Yip, Calvin K.
Jungbluth, Heinz
Koy, Anne
Dafsari, Hormos Salimi
Novel Genetic and Phenotypic Expansion in GOSR2-Related Progressive Myoclonus Epilepsy
title Novel Genetic and Phenotypic Expansion in GOSR2-Related Progressive Myoclonus Epilepsy
title_full Novel Genetic and Phenotypic Expansion in GOSR2-Related Progressive Myoclonus Epilepsy
title_fullStr Novel Genetic and Phenotypic Expansion in GOSR2-Related Progressive Myoclonus Epilepsy
title_full_unstemmed Novel Genetic and Phenotypic Expansion in GOSR2-Related Progressive Myoclonus Epilepsy
title_short Novel Genetic and Phenotypic Expansion in GOSR2-Related Progressive Myoclonus Epilepsy
title_sort novel genetic and phenotypic expansion in gosr2-related progressive myoclonus epilepsy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606070/
https://www.ncbi.nlm.nih.gov/pubmed/37895210
http://dx.doi.org/10.3390/genes14101860
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