Academic Journal
Novel Homozygous Truncating Variant Widens the Spectrum of Early-Onset Multisystemic SYNE1 Ataxia
| العنوان: | Novel Homozygous Truncating Variant Widens the Spectrum of Early-Onset Multisystemic SYNE1 Ataxia |
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| المؤلفون: | Karlsson, William Kristian, Højgaard, Joan Lilja Sunnleyg, Vilhelmsen, Anna, Crone, Clarissa, Andersen, Birgit, Law, Ian, Møller, Lisbeth Birk, Nielsen, Troels Tolstrup, Nielsen, Emilie Neerup, Krag, Thomas, Svenstrup, Kirsten, Nielsen, Jørgen Erik |
| المصدر: | Karlsson , W K , Højgaard , J L S , Vilhelmsen , A , Crone , C , Andersen , B , Law , I , Møller , L B , Nielsen , T T , Nielsen , E N , Krag , T , Svenstrup , K & Nielsen , J E 2022 , ' Novel Homozygous Truncating Variant Widens the Spectrum of Early-Onset Multisystemic SYNE1 Ataxia ' , Cerebellum , vol. 21 , no. 3 , pp. 514-519 . https://doi.org/10.1007/s12311-021-01308-w |
| سنة النشر: | 2022 |
| المجموعة: | University of Copenhagen: Research / Forskning ved Københavns Universitet |
| مصطلحات موضوعية: | Ataxia, Autosomal recessive, Cerebellum, Nesprin, Spinocerebellar ataxia, SYNE1 |
| الوصف: | Pathogenic variants in the SYNE1 gene are associated with a phenotypic spectrum spanning from late-onset, slowly progressive, relatively pure ataxia to early-onset, fast progressive multisystemic disease. Since its first description in 2007 as an adult-onset ataxia in French Canadian families, subsequent identification of patients worldwide has widened the clinical spectrum and increased the number of identified pathogenic variants. We report a 20-year-old Faroese female with early-onset progressive gait problems, weakness, dysphagia, slurred speech, orthostatic dizziness, and urge incontinence. Neurological examination revealed mild cognitive deficits, dysarthria, broken slow pursuit, hypometric saccades, weakness with spasticity, hyperreflexia, absent ankle reflexes, ataxia, and wide-based, spastic gait. Magnetic resonance imaging displayed atrophy of the cerebellum, brainstem, and spinal cord. Severely prolonged central motor conduction time and lower motor neuron involvement was demonstrated electrophysiologically. Fluorodeoxyglucose-positron emission tomography (FDG-PET) scan showed hypometabolism of the cerebellum and right frontal lobe. Muscle biopsy revealed chronic neurogenic changes and near-absent immunostaining for Nesprin-1. Next-generation sequencing revealed a previously undescribed homozygous truncating, likely pathogenic variant in the SYNE1 gene. The patient’s mother and paternal grandfather were heterozygous carriers of the variant. Her father’s genotype was unobtainable. We expand the list of likely pathogenic variants in SYNE1 ataxia with a novel homozygous truncating variant with proximity to the C-terminus and relate it to a phenotype comprising early-onset cerebellar deficits, upper and lower motor neuron involvement and cognitive deficits. Also, we report novel findings of focally reduced frontal lobe FDG-PET uptake and motor evoked potential abnormalities suggestive of central demyelination. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1007/s12311-021-01308-w |
| الاتاحة: | https://researchprofiles.ku.dk/da/publications/novel-homozygous-truncating-variant-widens-the-spectrum-of-earlyonset-multisystemic-syne1-ataxia(6f258086-ddad-49d4-a973-0b38d4686132).html https://doi.org/10.1007/s12311-021-01308-w |
| Rights: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.5679DF2C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1007/s12311-021-01308-w |
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