Early-Onset and Severe Complex Hereditary Spastic Paraplegia Caused by De Novo Variants in SPAST
| العنوان: | Early-Onset and Severe Complex Hereditary Spastic Paraplegia Caused by De Novo Variants in SPAST |
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| المؤلفون: | Alisa Mo, Afshin Saffari, Melanie Kellner, Marion Döbler‐Neumann, Catherine Jordan, Siddharth Srivastava, Bo Zhang, Mustafa Sahin, John K. Fink, Linsley Smith, Jennifer E. Posey, Katharine E. Alter, Camilo Toro, Craig Blackstone, Ariane G. Soldatos, Michelle Christie, Rebecca Schüle, Darius Ebrahimi‐Fakhari |
| المصدر: | Movement disorders 37(12), 2440-2446 (2022). doi:10.1002/mds.29225 Mov Disord |
| بيانات النشر: | Wiley, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Adult, cerebral palsy, Spastin, Adolescent, Spastic Paraplegia, Hereditary, childhood-onset movement disorders, Article, diagnosis [Spastic Paraplegia, Hereditary], Young Adult, Cross-Sectional Studies, Phenotype, Neurology, Muscle Spasticity, Child, Preschool, genetics [Spastic Paraplegia, Hereditary], Mutation, Humans, genetics [Spastin], SPAST, Neurology (clinical), ddc:610, hereditary spastic paraplegia, Child, neurogenetics |
| الوصف: | Familial hereditary spastic paraplegia (HSP)-SPAST (SPG4) typically presents with a pure HSP phenotype.The aim of this study was to delineate the genotypic and phenotypic spectrum of children with de novo HSP-SPAST.This study used a systematic cross-sectional analysis of clinical and molecular features.We report the clinical and molecular spectrum of 40 patients with heterozygous pathogenic de novo variants in SPAST (age range: 2.2-27.7 years). We identified 19 unique variants (16/40 carried the same recurrent variant, p.Arg499His). Symptom onset was in early childhood (median: 11.0 months, interquartile range: 6.0 months) with significant motor and speech delay, followed by progressive ascending spasticity, dystonia, neurogenic bladder dysfunction, gastrointestinal dysmotility, and epilepsy. The mean Spastic Paraplegia Rating Scale score was 32.8 ± 9.7 (standard deviation).These results confirm that de novo variants in SPAST lead to a severe and complex form of HSP that differs from classic familial pure HSP-SPAST. Clinicians should be aware of this syndrome in the differential diagnosis for cerebral palsy. © 2022 International Parkinson and Movement Disorder Society. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fb27dd83920485e0a4b88794a230e52cTest https://pub.dzne.de/record/165247Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fb27dd83920485e0a4b88794a230e52c |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |