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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10606070 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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