scholarly journals Identification of a novel mutation in ATP13A2 associated with a complicated form of hereditary spastic paraplegia

2020 ◽  
Vol 6 (5) ◽  
pp. e514
Author(s):  
Yasuko Odake ◽  
Kishin Koh ◽  
Yoshihisa Takiyama ◽  
Hiroyuki Ishiura ◽  
Shoji Tsuji ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Sequence Analysis ◽  
Hereditary Spastic Paraplegia ◽  
Psychiatric Symptoms ◽  
Spastic Paraparesis ◽  
Spastic Paraplegia ◽  
Caudate Nuclei ◽  
Extrapyramidal Signs ◽  
Complicated Form ◽  
Exome Sequence

ObjectiveTo establish molecular diagnosis for a family with a complicated form of autosomal recessive hereditary spastic paraplegia with intellectual disability, cognitive decline, psychosis, peripheral neuropathy, upward gaze palsy, and thin corpus callosum (TCC).MethodsPhysical examinations, laboratory tests, structural neuroimaging studies, and exome sequence analysis were carried out.ResultsThe 3 patients exhibited intellectual disability and progressive intellectual decline accompanied by psychiatric symptoms. Gait difficulty with spasticity and pyramidal weakness appeared at the ages of 20s–30s. Brain MRI revealed TCC with atrophic changes in the frontotemporal lobes, caudate nuclei, and cerebellum. Exome sequence analysis revealed a novel homozygous c.2654C>A (p. Ala885Asp) variant in the ATP13A2, a gene responsible for a complicated form of hereditary spastic paraplegia (SPG78), Kufor-Rakeb syndrome, and neuronal ceroid lipofuscinosis. The predominant clinical presentations of the patients include progressive intellectual disability and gait difficulty with spasticity and pyramidal weakness, consistent with the diagnosis of SPG78. Of note, prominent psychiatric symptoms and extrapyramidal signs including rigidity, dystonia, and involuntary movements preceded the spastic paraparesis.ConclusionsOur study further broadens the clinical spectrum associated with ATP13A2 mutations.

Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35)

2010 ◽  
Vol 31 (4) ◽  
pp. E1251-E1260 ◽  
Author(s):  
Katherine J. Dick ◽  
Matthias Eckhardt ◽  
Coro Paisán-Ruiz ◽  
Aisha Alkhayat Alshehhi ◽  
Christos Proukakis ◽  
...  
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Spastic Paraplegia ◽  
Complicated Form

scholarly journals Hereditary spastic paraplegia associated with thin corpus callosum

2001 ◽  
Vol 59 (3B) ◽  
pp. 790-792 ◽  
Author(s):  
Hélio A. Ghizoni Teive ◽  
Fabio Massaiti Iwamoto ◽  
Marcus Vinícius Della Coletta ◽  
Carlos Henrique Camargo ◽  
Ruth Danielle Bezerra ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Hereditary Spastic Paraplegia ◽  
Autosomal Recessive ◽  
Spastic Paraparesis ◽  
Japanese Patients ◽  
Genetic Profile ◽  
Spastic Paraplegia ◽  
Thin Corpus Callosum ◽  
Mental Deterioration ◽  
Magnetic Resonance Imaging Mri

Autosomal recessive hereditary spastic paraplegia (AR-HSP) associated with thin corpus callosum was recently described in Japan, and most families were linked to chromosome 15q13-15. We report two patients from two different Brazilian families with progressive gait disturbance starting at the second decade of life, spastic paraparesis, and mental deterioration. One patient presented cerebellar ataxia. Magnetic resonance imaging (MRI) of the head of both patients showed a thin corpus callosum. AR-HSP with a thin corpus callosum is a rare disorder, mainly described in Japanese patients. We found only 4 Caucasian families with AR-HSP with thin corpus callosum described in the literature. Further studies including additional Caucasian families of AR-HSP with thin corpus callosum are required to delineate the genetic profile of this syndrome in occidental countries.

scholarly journals Machado-Joseph disease versus hereditary spastic paraplegia: case report

2001 ◽  
Vol 59 (3B) ◽  
pp. 809-811 ◽  
Author(s):  
Hélio A. Ghizoni Teive ◽  
Fabio Massaiti Iwamoto ◽  
Carlos Henrique Camargo ◽  
Iscia Lopes-Cendes ◽  
Lineu Cesar Werneck
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Autosomal Dominant ◽  
Phenotypic Variability ◽  
Spastic Paraparesis ◽  
Japanese Patients ◽  
Cag Repeats ◽  
Spastic Paraplegia ◽  
Expanded Allele ◽  
Machado Joseph Disease ◽  
Autosomal Dominant Spinocerebellar Ataxia

Machado-Joseph disease (MJD) is the most common autosomal dominant spinocerebellar ataxia and presents great phenotypic variability. MJD presenting with spastic paraparesis was recently described in Japanese patients. We report the case of 41-year-old woman with the phenotype of complicated hereditary spastic paraplegia. Her father died at the age of 56 years due to an undiagnosed progressive neurological disease that presented parkinsonism. She had an expanded allele with 66 CAG repeats and a normal allele with 22 repeats in the gene of MJD. MJD should be considered in the differential diagnosis of autosomal dominant complicated HSP. A patient with the phenotype of complicated HSP and relatives with other clinical features of a neurodegenerative disease should raise the suspicion of MJD.

PLA2G6-associated neurodegeneration presenting as a complicated form of hereditary spastic paraplegia

2018 ◽  
Vol 64 (1) ◽  
pp. 55-59 ◽  
Author(s):  
Kishin Koh ◽  
◽  
Yuta Ichinose ◽  
Hiroyuki Ishiura ◽  
Haitian Nan ◽  
...  
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Spastic Paraplegia ◽  
Complicated Form

scholarly journals Truncating mutation in intracellular phospholipase A1 gene (DDHD2) in hereditary spastic paraplegia with intellectual disability (SPG54)

2015 ◽  
Vol 8 (1) ◽  
Author(s):  
Nuha Alrayes ◽  
Hussein Sheikh Ali Mohamoud ◽  
Musharraf Jelani ◽  
Saleem Ahmad ◽  
Nirmal Vadgama ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Hereditary Spastic Paraplegia ◽  
Spastic Paraplegia ◽  
Phospholipase A1 ◽  
Truncating Mutation

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

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.

scholarly journals A heterozygous mutation in the CCDC88C gene likely causes early-onset pure hereditary spastic paraplegia: a case report

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ashraf Yahia ◽  
Zhefan Stephen Chen ◽  
Ammar E. Ahmed ◽  
Sara Emad ◽  
Rawaa Adil ◽  
...  
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Early Onset ◽  
Late Onset ◽  
In Silico Analysis ◽  
Spinocerebellar Ataxia Type ◽  
Heterozygous Mutation ◽  
Spastic Paraplegia ◽  
Case Presentation ◽  
293 Cells ◽  
Extrapyramidal Signs

Abstract Background CCDC88C is a ubiquitously expressed protein with multiple functions, including roles in cell polarity and the development of dendrites in the nervous system. Bi-allelic mutations in the CCDC88C gene cause autosomal recessive congenital hydrocephalus (OMIM #236600). Studies recently linked heterozygous mutations in CCDC88C to the development of the late-onset spinocerebellar ataxia type 40 (OMIM #616053). Case presentation A 48-year-old Sudanese female presented with pure early onset hereditary spastic paraplegia. Exome sequencing, in-silico analysis, and Sanger sequencing identified the heterozygous NM_001080414.4:c.1993G > A (p.E665K) variant in CCDC88C as a potential cause of her illness. To explore the pathogenicity of the NM_001080414.4:c.1993G > A (p.E665K) variant, we expressed it in human embryonic kidney 293 cells and assessed its effects on apoptosis. In our experiment, NM_001080414.4:c.1993G > A (p.E665K) induced JNK hyper-phosphorylation and enhanced apoptosis. In contrast to previous reports, our patient developed neurological symptoms in early childhood and showed neither features of cerebellar ataxia, extrapyramidal signs, nor evidence of intellectual involvement. Conclusion We, herein, heighlighted the possibility of extending the phenotype associated with variants in CCDC88C to include early-onset pure hereditary spastic paraplegia.

scholarly journals 046 A critical review of biomarkers for hereditary spastic paraplegia

2019 ◽  
Vol 90 (e7) ◽  
pp. A15.3-A16
Author(s):  
Sue-Faye Siow ◽  
Gautam Wali ◽  
Carolyn Sue ◽  
Kishore R Kumar
Keyword(s):  
Disease Severity ◽  
Hereditary Spastic Paraplegia ◽  
Rating Scales ◽  
Diffusion Tensor ◽  
Spastic Paraparesis ◽  
Spastic Paraplegia ◽  
Limb Weakness ◽  
Disease Modifying Therapy ◽  
Small Patient ◽  
Potential Biomarkers

IntroductionHereditary spastic paraplegia (HSP) is a rare neurodegenerative condition characterised by lower limb weakness and spasticity. Currently, treatment is symptomatic and there is no disease modifying therapy. Though candidate therapeutic agents have been identified, sensitive biomarkers to measure treatment efficacy in clinical drug trials are lacking. There are many challenges in the search for appropriate biomarkers including the rarity of HSP, clinical and genetic heterogeneity of HSP and slow disease progression.MethodsWe performed a search on PubMed and Medline using the search terms (‘hereditary spastic paraplegia’ OR ‘spastic paraparesis’) AND ‘biomarker*’. We searched the reference lists of relevant articles to identify further studies. We collected data on number of participants, HSP genotype, methodology, and outcomes.Results72 papers were identified: 2 on Rating scales, 9 on gait analysis, 33 on neurophysiological measures, 23 on neuroimaging markers and 5 on biochemical markers. The studies reviewed demonstrated variation in methodologies and outcomes, including mixed genotype (41/72 papers) and genotype-specific (31/72 papers) patient cohorts, varied neurophysiological techniques and different outcome measures. 68/72 studies reviewed had small patient numbers (<50 patients). All potential biomarkers reviewed were able to differentiate HSP patients from controls. Only diffusion tensor imaging (DTI) parameters showed significant correlation with disease severity.ConclusionAlthough useful as diagnostic biomarkers, further studies are required to evaluate these potential biomarkers longitudinally and to assess their reliability as surrogates for underlying neurodegenerative changes and clinical disease severity. DTI showed the most promise as a biomarker for disease severity in HSP.

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