scholarly journals Case report on novel mutation in SPAST gene in Polish family with spastic paraplegia

BMC Neurology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Aleksandra Klimkowicz-Mrowiec ◽  
Anna Dziubek ◽  
Malgorzata Sado ◽  
Marek Karpiński ◽  
Agnieszka Gorzkowska
Keyword(s):  
Case Report ◽  
Genetic Testing ◽  
Family History ◽  
Lower Limb ◽  
Hereditary Spastic Paraplegia ◽  
Novel Mutation ◽  
Family Members ◽  
Spastic Paraplegia ◽  
Limb Spasticity ◽  
Lower Limb Spasticity

Abstract Background Hereditary spastic paraplegia is a large group of degenerative, neurological disorders characterized by progressive lower limb spasticity and weakness. The disease was investigated precisely but still clinicians often make incorrect or late diagnosis. Our aim was to investigate the genetic background and clinical phenotype of spastic paraplegia in large Polish family. Case presentation A 37 years old woman presented with 4-year history of walking difficulties. On neurological examination, she had signs of upper motor lesion in lower extremities. She denied sphincter dysfunction and her cognition was normal. Her family history was positive for individuals with gait problems. The initial diagnosis was familial spastic paraplegia. Genetic testing identified a novel mutation in SPAST gene. All available family members were examined and had genetic testing. The same mutation in SPAST gene was identified in other affected family members. All patients caring the mutation presented with different phenotypes. Conclusion This study presents a family with spastic paraplegia due to a novel mutation c.1390G›T(p.Glu464Term) in SPAST gene. Affected individuals showed a range of phenotypes that varied in their severity. This case report demonstrates, the signs of hereditary spastic paraplegia can be often misdiagnosed with other diseases. Therefore genetic testing should always be considered in patients with lower limb spasticity and positive family history in order to help to establish the correct diagnosis.

scholarly journals Phenoconversion from Spastic Paraplegia to ALS/FTD Associated with CYP7B1 Compound Heterozygous Mutations

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1876
Author(s):  
Julian Theuriet ◽  
Antoine Pegat ◽  
Pascal Leblanc ◽  
Sandra Vukusic ◽  
Cécile Cazeneuve ◽  
...  
Keyword(s):  
Lower Limb ◽  
Clinical Symptoms ◽  
Compound Heterozygous ◽  
Spastic Paraplegia ◽  
The Third ◽  
Limb Spasticity ◽  
Lower Limb Spasticity ◽  
Compound Heterozygous Mutations ◽  
Biallelic Mutations ◽  
Lateral Sclerosis

Biallelic mutations in the CYP7B1 gene lead to spastic paraplegia-5 (SPG5). We report herein the case of a patient whose clinical symptoms began with progressive lower limb spasticity during childhood, and who secondly developed amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) at the age of 67 years. Hereditary spastic paraplegia (HSP) gene analysis identified the compound heterozygous mutations c.825T>A (pTyr275*) and c.1193C>T (pPro398Leu) in CYP7B1 gene. No other pathogenic variant in frequent ALS/FTD causative genes was found. The CYP7B1 gene seems, therefore, to be the third gene associated with the phenoconversion from HSP to ALS, after the recently described UBQLN2 and ERLIN2 genes. We therefore expand the phenotype associated with CYP7B1 biallelic mutations and make an assumption about a link between cholesterol dyshomeostasis and ALS/FTD.

scholarly journals Pathogenic Variants in ABHD16A Cause a Novel Psychomotor Developmental Disorder With Spastic Paraplegia

2021 ◽  
Vol 12 ◽  
Author(s):  
Ashraf Yahia ◽  
Liena E. O. Elsayed ◽  
Remi Valter ◽  
Ahlam A. A. Hamed ◽  
Inaam N. Mohammed ◽  
...  
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Loss Of Function ◽  
Spastic Paraplegia ◽  
Cellular Processes ◽  
Pathogenic Variants ◽  
Neurological Phenotype ◽  
Limb Spasticity ◽  
Lower Limb Spasticity ◽  
Generation Sequencing

Introduction: Hereditary spastic paraplegia is a clinically and genetically heterogeneous neurological entity that includes more than 80 disorders which share lower limb spasticity as a common feature. Abnormalities in multiple cellular processes are implicated in their pathogenesis, including lipid metabolism; but still 40% of the patients are undiagnosed. Our goal was to identify the disease-causing variants in Sudanese families excluded for known genetic causes and describe a novel clinico-genetic entity.Methods: We studied four patients from two unrelated consanguineous Sudanese families who manifested a neurological phenotype characterized by spasticity, psychomotor developmental delay and/or regression, and intellectual impairment. We applied next-generation sequencing, bioinformatics analysis, and Sanger sequencing to identify the genetic culprit. We then explored the consequences of the identified variants in patients-derived fibroblasts using targeted-lipidomics strategies.Results and Discussion: Two homozygous variants in ABHD16A segregated with the disease in the two studied families. ABHD16A encodes the main brain phosphatidylserine hydrolase. In vitro, we confirmed that ABHD16A loss of function reduces the levels of certain long-chain lysophosphatidylserine species while increases the levels of multiple phosphatidylserine species in patient's fibroblasts.Conclusion:ABHD16A loss of function is implicated in the pathogenesis of a novel form of complex hereditary spastic paraplegia.

Autosomal recessive hereditary spastic paraplegia: a rare case of a family with phenotypic variation

2020 ◽  
Vol 17 ◽  
Author(s):  
Mor Saban ◽  
Tal Shachar
Keyword(s):  
Genetic Testing ◽  
Phenotypic Variation ◽  
Hereditary Spastic Paraplegia ◽  
Neurodegenerative Disorder ◽  
Age Of Onset ◽  
Treatment Options ◽  
Family Members ◽  
Complex Form ◽  
Single Family ◽  
Spastic Paraplegia

Background: Hereditary spastic paraplegia is a neurodegenerative disorder with a pure and complex form. More than 50 genetic types are currently known, with different ages of onset for characteristic symptoms. Data regarding hereditary spastic paraplegia remain scarce, and the rare subtype of spastic paraplegia type 5 is no exception. Objective: This report presents data regarding the case of a single family, from the city of Djerba, with five individuals affected with hereditary spastic paraplegia, the largest number of spastic paraplegia type 5 mutated family members so far reported in current literature. Methods: To emphasize the importance of genetic testing, we retrospectively reviewed a familial confirmed case of hereditary spastic paraplegia. Clinical features of family members were described. Results: The family presents a large phenotypic variation that in part differs from the known phenotypic presentations. Age of onset and clinical manifestation showed interfamilial variations. The alteration found in CYP7B1 (c.1081C>T; p.R361*) may help emphasize the importance of genetic testing and the much-needed treatment options already in use in current neurological practice. Conclusion: The understanding of the molecular pathways of hereditary spastic paraplegia, together with the establishment of disease biomarkers, will hopefully lead to better, and more personalized treatment.

scholarly journals Bilateral L2 dorsal root ganglion-stimulation suppresses lower limb spasticity following chronic motor complete Spinal Cord Injury: A case report

2020 ◽  
Vol 13 (3) ◽  
pp. 637-639
Author(s):  
Sadaf Soloukey ◽  
Judith Drenthen ◽  
Rutger Osterthun ◽  
Judith D. de Rooij ◽  
Chris I. De Zeeuw ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Case Report ◽  
Dorsal Root Ganglion ◽  
Lower Limb ◽  
Dorsal Root ◽  
Cord Injury ◽  
Limb Spasticity ◽  
Lower Limb Spasticity ◽  
Complete Spinal Cord Injury

scholarly journals A Japanese hereditary spastic paraplegia family with a rare nonsynonymous variant in the SPAST gene

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Takuya Morikawa ◽  
Shiroh Miura ◽  
Takahisa Tateishi ◽  
Kazuhito Noda ◽  
Hiroki Shibata
Keyword(s):  
Molecular Diagnosis ◽  
Hereditary Spastic Paraplegia ◽  
Autosomal Dominant ◽  
Family Members ◽  
Pathogenic Variant ◽  
Lower Limbs ◽  
Spastic Paraplegia ◽  
Nonsynonymous Variant ◽  
Japanese Family ◽  
Functional Variants

AbstractSpastic paraplegia (SPG) type 4 is an autosomal dominant SPG caused by functional variants in the SPAST gene. We examined a Japanese family with three autosomal dominant SPG patients. These patients presented with typical symptoms of SPG, such as spasticity of the lower limbs. We identified a rare nonsynonymous variant, NM_014946.4:c.1252G>A [p.Glu418Lys], in all three family members. This variant has previously been reported in a Russian SPG family as a “likely pathogenic” variant.5 Ascertainment of additional patients carrying this variant in an unrelated Japanese SPG family further supports its pathogenicity. Molecular diagnosis of SPG4 in this family with hereditary spastic paraplegia is confirmed.

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