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

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

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.

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 Autosomal dominant hereditary spastic paraplegia: DHPLC-based mutation analysis ofSPG4 reveals eleven novel mutations

2005 ◽  
Vol 25 (5) ◽  
pp. 506-506 ◽  
Author(s):  
Clarice Patrono ◽  
Valentina Scarano ◽  
Federica Cricchi ◽  
Mariarosa A. B. Melone ◽  
Maria Chiriaco ◽  
...  
Keyword(s):  
Mutation Analysis ◽  
Hereditary Spastic Paraplegia ◽  
Autosomal Dominant ◽  
Spastic Paraplegia ◽  
Novel Mutations

A novel locus for autosomal dominant “uncomplicated” hereditary spastic paraplegia maps to chromosome 8p21.1-q13.3

2007 ◽  
Vol 122 (3-4) ◽  
pp. 261-273 ◽  
Author(s):  
Sylvain Hanein ◽  
Alexandra Dürr ◽  
Pascale Ribai ◽  
Sylvie Forlani ◽  
Anne-Louise Leutenegger ◽  
...  
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Autosomal Dominant ◽  
Spastic Paraplegia

scholarly journals High frequency of SPG4 in Taiwanese families with autosomal dominant hereditary spastic paraplegia

BMC Neurology ◽  
2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Min-Yu Lan ◽  
Yung-Yee Chang ◽  
Tu-Hseuh Yeh ◽  
Szu-Chia Lai ◽  
Chia-Wei Liou ◽  
...  
Keyword(s):  
High Frequency ◽  
Hereditary Spastic Paraplegia ◽  
Autosomal Dominant ◽  
Spastic Paraplegia
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