Novel Genetic and Phenotypic Expansion in GOSR2-Related Progressive Myoclonus Epilepsy
(2023) In Genes 14(10).- Abstract
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,... (More)
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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- author
- Hentrich, Lea ; Parnes, Mered ; Lotze, Timothy Edward ; Coorg, Rohini ; de Koning, Tom J LU ; Nguyen, Kha M ; Yip, Calvin K ; Jungbluth, Heinz ; Koy, Anne and Dafsari, Hormos Salimi
- organization
- publishing date
- 2023-09-25
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adolescent, Child, Child, Preschool, Female, Humans, Male, Ataxia/genetics, Dystonia, Dystonic Disorders, Mutation, Myoclonic Epilepsies, Progressive/genetics, Myoclonus, Qb-SNARE Proteins/genetics, Seizures
- in
- Genes
- volume
- 14
- issue
- 10
- article number
- 1860
- publisher
- MDPI AG
- external identifiers
-
- scopus:85175274764
- pmid:37895210
- ISSN
- 2073-4425
- DOI
- 10.3390/genes14101860
- language
- English
- LU publication?
- yes
- id
- 658a6065-21cd-4175-b5f4-a63ef234b401
- date added to LUP
- 2023-11-15 13:46:41
- date last changed
- 2024-04-27 19:51:04
@article{658a6065-21cd-4175-b5f4-a63ef234b401,
abstract = {{<p>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. </p>}},
author = {{Hentrich, Lea and Parnes, Mered and Lotze, Timothy Edward and Coorg, Rohini and de Koning, Tom J and Nguyen, Kha M and Yip, Calvin K and Jungbluth, Heinz and Koy, Anne and Dafsari, Hormos Salimi}},
issn = {{2073-4425}},
keywords = {{Adolescent; Child; Child, Preschool; Female; Humans; Male; Ataxia/genetics; Dystonia; Dystonic Disorders; Mutation; Myoclonic Epilepsies, Progressive/genetics; Myoclonus; Qb-SNARE Proteins/genetics; Seizures}},
language = {{eng}},
month = {{09}},
number = {{10}},
publisher = {{MDPI AG}},
series = {{Genes}},
title = {{Novel Genetic and Phenotypic Expansion in GOSR2-Related Progressive Myoclonus Epilepsy}},
url = {{http://dx.doi.org/10.3390/genes14101860}},
doi = {{10.3390/genes14101860}},
volume = {{14}},
year = {{2023}},
}