A complex form of hereditary spastic paraplegia harboring a novel variant, p.W1515*, in the SPG11 gene

Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurological disorders that are characterized by progressive spasticity of the lower extremities. It can present as pure form or complex form. It can be present from infancy to adulthood, but majority in adult population. Childhood onset HSP must be differentiated from common conditions like cerebral palsy, neurodegenerative disorders and metabolic disorders. Many patients with pediatric HSP are mistakenly diagnosed with cerebral palsy. In children with spastic paraplegia in whom no acquired cause identified, HSP should be considered. Here we diagnosed a 6-year-old boy with HSP who presented with progressive spastic paraplegia, intellectual disability, seizures, joint contractures and cataract. His genetic study revealed exonic deletion of endoplasmic reticulum lipid raft-associated protein gene, which is associated with complicated Autosomal recessive HSP 18 (SPG18). HSP 18 was rarely described in literature.

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CAPN1 and hereditary spastic paraplegia: a novel variant in an Iranian family and overview of the genotype-phenotype correlation

International Journal of Neuroscience ◽

10.1080/00207454.2020.1763344 ◽

2020 ◽

pp. 1-13

Author(s):

Mohammad Masoud Rahimi Bidgoli ◽

Leila Javanparast ◽

Mohammad Rohani ◽

Hossein Najmabadi ◽

Babak Zamani ◽

...

Keyword(s):

Hereditary Spastic Paraplegia ◽

Spastic Paraplegia ◽

Phenotype Correlation ◽

Genotype Phenotype Correlation ◽

Iranian Family ◽

Novel Variant

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A Novel SPAST/SPG4 Splice-Site Variant in a Family with Dominant Hereditary Spastic Paraplegia

Case Reports in Neurological Medicine ◽

10.1155/2020/7219514 ◽

2020 ◽

Vol 2020 ◽

pp. 1-3

Author(s):

Nathaniel M. Robbins ◽

Jillian R. Ozmore ◽

Thomas L. Winder ◽

Pedro Gonzalez-Alegre ◽

Tanya M. Bardakjian

Keyword(s):

Splice Site ◽

Hereditary Spastic Paraplegia ◽

Spastic Paraparesis ◽

Spastic Paraplegia ◽

Novel Variant ◽

Consensus Splice Site ◽

Diagnostic Work ◽

Next Generation Sequencing Ngs ◽

Work Up

Some causes of spastic paraplegia are treatable and many are not. Diagnostic work-up to determine the etiology can be costly and invasive. Here we report the case of a man with slowly progressive spastic paraparesis. Using a multigene next-generation sequencing (NGS) panel, we identified a novel variant in the consensus splice site of the SPAST gene (exon 13, c.1536G>A, heterozygous), affecting codon 512 of the SPAST mRNA. The observed variant segregated with the disease in four tested family members. In this case, genetic confirmation obviated the need for additional testing such as MRI and lumbar puncture and helped the patient and his family understand his condition and prognosis. We conclude with a brief discussion of the SPG4/SPAST gene and the role of multigene panels in the diagnosis and management of hereditary spastic paraplegia.

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

Current Pharmacogenomics and Personalized Medicine ◽

10.2174/1875692117999201211142908 ◽

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.

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