scholarly journals NIPA1 Gene Mutations Cause Autosomal Dominant Hereditary Spastic Paraplegia (SPG6)

2003 ◽  
Vol 73 (4) ◽  
pp. 967-971 ◽  
Author(s):  
Shirley Rainier ◽  
Jing-Hua Chai ◽  
Debra Tokarz ◽  
Robert D. Nicholls ◽  
John K. Fink
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Autosomal Dominant ◽  
Gene Mutations ◽  
Spastic Paraplegia

Further evidence thatSPG3A gene mutations cause autosomal dominant hereditary spastic paraplegia

2002 ◽  
Vol 51 (6) ◽  
pp. 794-795 ◽  
Author(s):  
Maria Muglia ◽  
Angela Magariello ◽  
Giuseppe Nicoletti ◽  
Alessandra Patitucci ◽  
Anna Lia Gabriele ◽  
...  
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Autosomal Dominant ◽  
Gene Mutations ◽  
Spastic Paraplegia

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 Novel SPG 11 Mutations in Hereditary Spastic Paraplegia With Thin Corpus Callosum in a Chinese Family

2016 ◽  
Vol 43 (6) ◽  
pp. 833-840
Author(s):  
Xiaojie Tian ◽  
Min Wang ◽  
Kaiyuan Zhang ◽  
Xinqing Zhang
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Gene Mutations ◽  
Protein Product ◽  
Exome Capture ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Spastic Paraplegia ◽  
Reading Frame ◽  
Physical Examinations ◽  
Compound Heterozygous Mutations

AbstractBackground: Hereditary spastic paraplegia (HSP) is a neurodegenerative disease that is characterized by progressive weakness and spasticity of the lower extremities; HSP can present as complicated forms with additional neurological signs. More than 70 disease loci have been described with different modes of inheritance. Methods: In this study, nine subjects from a Chinese family that included two individuals affected by HSP were examined through detailed clinical evaluations, physical examinations, and genetic tests. Targeted exome capture technology was used to identify gene mutations. Results: Two novel compound heterozygous mutations in the SPG 11 gene were identified, c.4001_4002insATAAC and c.4057C>G. The c.4001_4002insATAAC mutation leads to a reading frame shift during transcription, resulting in premature termination of the protein product. The missense mutation c.4057C>G (p.H1353D) is located in a highly conserved domain and is predicted to be a damaging substitution. Conclusions: Based on the results described here, we propose that these novel compound heterozygous mutations in SPG 11 are the genetic cause of autosomal recessive HSP in this Chinese family.

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

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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