scholarly journals A novel missense mutation (I344K) in the SPG4 gene in a Korean family with autosomal-dominant hereditary spastic paraplegia

2002 ◽  
Vol 47 (9) ◽  
pp. 473-477 ◽  
Author(s):  
C.-S. Ki ◽  
W. Y. Lee ◽  
D. H. Han ◽  
D. H. Sung ◽  
K.-B. Lee ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Hereditary Spastic Paraplegia ◽  
Autosomal Dominant ◽  
Spastic Paraplegia ◽  
Korean Family

scholarly journals Missense mutation of SPAST protein (I344K) results in loss of ATPase activity and prolonged the half-life, implicated in autosomal dominant hereditary spastic paraplegia

2018 ◽  
Vol 1864 (10) ◽  
pp. 3221-3233 ◽  
Author(s):  
Jung Hwa Lim ◽  
Hyun Mi Kang ◽  
Hong-Ryul Jung ◽  
Dae-Soo Kim ◽  
Kyung Hee Noh ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Missense Mutation ◽  
Hereditary Spastic Paraplegia ◽  
Half Life ◽  
Autosomal Dominant ◽  
Spastic Paraplegia

scholarly journals Pathogenic Variant of REEP1 in a Korean Family with Autosomal-Dominant Hereditary Spastic Paraplegia

2018 ◽  
Vol 14 (2) ◽  
pp. 248 ◽  
Author(s):  
Hyung Jun Park ◽  
Myung Jun Lee ◽  
Jee Eun Lee ◽  
Kee Duk Park ◽  
Young-Chul Choi
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Autosomal Dominant ◽  
Pathogenic Variant ◽  
Spastic Paraplegia ◽  
Korean Family

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.

Mutation analysis of thespastingene (SPG4) in patients in Germany with autosomal dominant hereditary spastic paraplegia

2002 ◽  
Vol 20 (2) ◽  
pp. 127-132 ◽  
Author(s):  
S. Sauter ◽  
B. Miterski ◽  
S. Klimpe ◽  
D. Bönsch ◽  
L. Schöls ◽  
...  
Keyword(s):  
Mutation Analysis ◽  
Hereditary Spastic Paraplegia ◽  
Autosomal Dominant ◽  
Spastic Paraplegia

scholarly journals ACO2 homozygous missense mutation associated with complicated hereditary spastic paraplegia

2018 ◽  
Vol 4 (2) ◽  
pp. e223 ◽  
Author(s):  
Christian G. Bouwkamp ◽  
Zaid Afawi ◽  
Aviva Fattal-Valevski ◽  
Inge E. Krabbendam ◽  
Stefano Rivetti ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Hereditary Spastic Paraplegia ◽  
Krebs Cycle ◽  
Spastic Paraplegia ◽  
Homozygous Carrier ◽  
Clinical Genetic ◽  
Homozygous Missense Mutation ◽  
Recessive Mutations ◽  
Mitochondrial Aconitase ◽  
Essential Enzyme

ObjectiveTo identify the clinical characteristics and genetic etiology of a family affected with hereditary spastic paraplegia (HSP).MethodsClinical, genetic, and functional analyses involving genome-wide linkage coupled to whole-exome sequencing in a consanguineous family with complicated HSP.ResultsA homozygous missense mutation was identified in the ACO2 gene (c.1240T>G p.Phe414Val) that segregated with HSP complicated by intellectual disability and microcephaly. Lymphoblastoid cell lines of homozygous carrier patients revealed significantly decreased activity of the mitochondrial aconitase enzyme and defective mitochondrial respiration. ACO2 encodes mitochondrial aconitase, an essential enzyme in the Krebs cycle. Recessive mutations in this gene have been previously associated with cerebellar ataxia.ConclusionsOur findings nominate ACO2 as a disease-causing gene for autosomal recessive complicated HSP and provide further support for the central role of mitochondrial defects in the pathogenesis of HSP.

Autosomal dominant hereditary spastic paraplegia caused by mutation of UBAP1

Neurogenetics ◽  
2020 ◽  
Vol 21 (3) ◽  
pp. 169-177
Author(s):  
Jianda Wang ◽  
Yanqi Hou ◽  
Lina Qi ◽  
Shuang Zhai ◽  
Liangwu Zheng ◽  
...  
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Autosomal Dominant ◽  
Spastic Paraplegia

scholarly journals Stop-gain mutations in UBAP1 cause pure autosomal-dominant spastic paraplegia

Brain ◽  
2019 ◽  
Vol 142 (8) ◽  
pp. 2238-2252 ◽  
Author(s):  
Xiang Lin ◽  
Hui-Zhen Su ◽  
En-Lin Dong ◽  
Xiao-Hong Lin ◽  
Miao Zhao ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Cortical Neurons ◽  
Hereditary Spastic Paraplegia ◽  
Autosomal Dominant ◽  
Wild Type Mouse ◽  
Spastic Paraplegia ◽  
Endosomal Sorting ◽  
Hereditary Spastic Paraplegias ◽  
Cultured Cortical Neurons

Abstract Hereditary spastic paraplegias refer to a heterogeneous group of neurodegenerative disorders resulting from degeneration of the corticospinal tract. Clinical characterization of patients with hereditary spastic paraplegias represents progressive spasticity, exaggerated reflexes and muscular weakness. Here, to expand on the increasingly broad pools of previously unknown hereditary spastic paraplegia causative genes and subtypes, we performed whole exome sequencing for six affected and two unaffected individuals from two unrelated Chinese families with an autosomal dominant hereditary spastic paraplegia and lacking mutations in known hereditary spastic paraplegia implicated genes. The exome sequencing revealed two stop-gain mutations, c.247_248insGTGAATTC (p.I83Sfs*11) and c.526G>T (p.E176*), in the ubiquitin-associated protein 1 (UBAP1) gene, which co-segregated with the spastic paraplegia. We also identified two UBAP1 frameshift mutations, c.324_325delCA (p.H108Qfs*10) and c.425_426delAG (p.K143Sfs*15), in two unrelated families from an additional 38 Chinese pedigrees with autosomal dominant hereditary spastic paraplegias and lacking mutations in known causative genes. The primary disease presentation was a pure lower limb predominant spastic paraplegia. In vivo downregulation of Ubap1 in zebrafish causes abnormal organismal morphology, inhibited motor neuron outgrowth, decreased mobility, and shorter lifespan. UBAP1 is incorporated into endosomal sorting complexes required for transport complex I and binds ubiquitin to function in endosome sorting. Patient-derived truncated form(s) of UBAP1 cause aberrant endosome clustering, pronounced endosome enlargement, and cytoplasmic accumulation of ubiquitinated proteins in HeLa cells and wild-type mouse cortical neuron cultures. Biochemical and immunocytochemical experiments in cultured cortical neurons derived from transgenic Ubap1flox mice confirmed that disruption of UBAP1 leads to dysregulation of both early endosome processing and ubiquitinated protein sorting. Strikingly, deletion of Ubap1 promotes neurodegeneration, potentially mediated by apoptosis. Our study provides genetic and biochemical evidence that mutations in UBAP1 can cause pure autosomal dominant spastic paraplegia.

Large deletion involving the 5?-UTR in the spastin gene caused mild phenotype of autosomal dominant hereditary spastic paraplegia

2005 ◽  
Vol 133A (1) ◽  
pp. 13-17 ◽  
Author(s):  
Hiroshi Iwanaga ◽  
Akira Tsujino ◽  
Susumu Shirabe ◽  
Hiroto Eguchi ◽  
Naomi Fukushima ◽  
...  
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Autosomal Dominant ◽  
Large Deletion ◽  
Spastic Paraplegia ◽  
Mild Phenotype
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