scholarly journals Cerebellar lncRNA Expression Profile Analysis of SCA3/MJD Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Zhe Long ◽  
Tianjiao Li ◽  
Zhao Chen ◽  
Yun Peng ◽  
Chunrong Wang ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Expression Profile ◽  
Profile Analysis ◽  
Cag Repeats ◽  
Spinocerebellar Ataxia Type ◽  
Coding Region ◽  
Spinocerebellar Ataxia Type 3 ◽  
Lncrna Expression ◽  
Expression Profile Analysis ◽  
Progressive Cerebellar Ataxia

Spinocerebellar ataxia type 3 (SCA3) or Machado-Joseph disease (MJD) is the most common autosomal dominant spinocerebellar ataxia in China with highly clinical heterogeneity, such as progressive cerebellar ataxia, dysarthria, pyramidal signs, external ophthalmoplegia, dysphagia, and distal muscle atrophy. It is caused by the abnormal expansion of CAG repeats in a coding region of ATXN3. However, by focusing on the ATXN3 itself cannot fully explain the heterogeneous clinical features of SCA3/MJD. With the discovery of the increasing number of long noncoding RNAs (lncRNAs) that are believed to be involved in spinocerebellar ataxia type 8 (SCA8) and Huntington disease (HD), we wonder whether the lncRNAs are differentially expressed in the SCA3/MJD patients compared to the nonpatients. As the first step, we used lncRNA-Seq to investigate differential expression of the lncRNAs in the SCA3/MJD mice. Two known lncRNAs, n297609 and n297477, and a novel lncRNA TCONS_00072962 have been identified in SCA3/MJD mice with abnormal expression. The first discovery of the novel lncRNA TCONS_00072962 enriched the lncRNA expression profile in the SCA3/MJD mouse model.

scholarly journals Homozygous spinocerebellar ataxia type 3 in China: a case report

2021 ◽  
Vol 49 (6) ◽  
pp. 030006052110213
Author(s):  
Yuchao Chen ◽  
Dan Li ◽  
Minger Wei ◽  
Menglu Zhou ◽  
Linan Zhang ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Clinical Phenotype ◽  
Gene Dosage ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Spinocerebellar Ataxia Type ◽  
Contraction Pattern ◽  
Spinocerebellar Ataxia Type 3 ◽  
Type 3 ◽  
Stable Transmission

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease caused by a heterozygous CAG repeat expansion in the ataxin 3 gene ( ATXN3). However, patients with homozygous SCA3 carrying expanded CAG repeats in both alleles of ATXN3 are extremely rare. Herein, we present a case of a 50-year-old female who had homozygous SCA3 with expansion of 62/62 repeats. Segregation analysis of the patient’s family showed both a contraction pattern of CAG repeat length and stable transmission. The present case demonstrated an earlier onset and more severe clinical phenotype than that seen in heterozygous individuals, suggesting that the gene dosage enhances disease severity.

scholarly journals Frequency of the different mutations causing spinocerebellar ataxia (SCA1, SCA2, MJD/SCA3 and DRPLA) in a large group of Brazilian patients

1997 ◽  
Vol 55 (3B) ◽  
pp. 519-529 ◽  
Author(s):  
Iscia Lopes-Cendesi ◽  
Hélio G.A. Teive ◽  
Maria E Calcagnotto ◽  
Jaderson C. da Costa ◽  
Francisco Cardoso ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Autosomal Dominant ◽  
Late Onset ◽  
Geographic Origin ◽  
Autosomal Dominant Inheritance ◽  
Cag Repeat ◽  
Spinocerebellar Ataxia Type ◽  
Dominant Inheritance ◽  
Coding Region ◽  
Spinocerebellar Ataxia Type 3

Spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2) and Machado-Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3) are three distinctive forms of autosomal dominant spinocerebellar ataxia (SCA) caused by expansions of an unstable CAG repeat localized in the coding region of the causative genes. Another related disease, dentatorubropallidoluysian atrophy (DRPLA) is also caused by an unstable triplet repeat and can present as SCA in late onset patients. We investigated the frequency of the SCA1, SCA2, MJD/SCA3 and DRPLA mutations in 328 Brazilian patients with SCA, belonging to 90 unrelated families with various patterns of inheritance and originating in different geographic regions of Brazil. We found mutations in 35 families (39%), 32 of them with a clear autosomal dominant inheritance. The frequency of the SCA1 mutation was 3% of all patients; and 6 % in the dominantly inherited SCAs. We identified the SCA2 mutation in 6% of all families and in 9% of the families with autosomal dominant inheritance. The MJD/SCA3 mutation was detected in 30 % of all patients; and in the 44% of the dominantly inherited cases. We found no DRPLA mutation. In addition, we observed variability in the frequency of the different mutations according to geographic origin of the patients, which is probably related to the distinct colonization of different parts of Brazil. These results suggest that SCA may be occasionally caused by the SCA1 and SCA2 mutations in the Brazilian population, and that the MJD/SCA3 mutation is the most common cause of dominantly inherited SCA in Brazil.

Molecular characteristics and expression profile of the Rheb gene in Rongchang piglets (Sus scrofa)

2015 ◽  
Author(s):  
Ling Gan ◽  
Hongyuan Mei ◽  
Binyu Yang ◽  
Fuyuan Zuo
Keyword(s):  
Salivary Gland ◽  
Expression Pattern ◽  
Expression Profile ◽  
Profile Analysis ◽  
Developmental Expression ◽  
Molecular Characteristics ◽  
Mrna Levels ◽  
Coding Region ◽  
Large White ◽  
Expression Profile Analysis

To give some insights into the genetic functions of Rheb signaling pathway in Rongchang piglets, this study reported the identification of complete coding sequence of the Rheb gene in Rongchang piglets and indicated that the complete coding region sequence is 555bp in length and encodes 184 amino acids, containing nearly all the conserved protein domains in the Rheb protein family. The deduced amino acid sequence identity between the Rongchang pig and sheep, cattle, or goat is 100%, 99% and 98%, respectively. Spatial transcriptional profile analysis indicated that the Rheb gene is expressed at remarkably high levels in both salivary gland and brain, especially in hypothalamus and ventral hippocampus (VH) regions of brain. Developmental expression profile analysis revealed the expression pattern is different between brain sub-regions and salivary gland of these two breeds of piglets, with the similar expression pattern despite various mRNA levels between Rongchang and Large White piglets.

scholarly journals CRISPR/Cas9-based silencing of the ATXN1 gene in Spinocerebellar ataxia type 1 (SCA1) fibroblasts

2020 ◽  
Author(s):  
Francesca Salvatori ◽  
Mariangela Pappadà ◽  
Mariaconcetta Sicurella ◽  
Mattia Buratto ◽  
Valentina Simioni ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Neurodegenerative Disorder ◽  
Cag Repeats ◽  
Spinocerebellar Ataxia Type ◽  
Rna Seq ◽  
Coding Region ◽  
Spinocerebellar Ataxia Type 1 ◽  
Polyq Tract

AbstractSpinocerebellar Ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by a gain-of-function protein with toxic activities, containing an expanded polyQ tract in the coding region. Actually, there are no treatments available to delay the onset, stop or slow down the progression of this pathology. Many approaches developed over the years involve the use of siRNAs and antisense oligonucleotides (ASOs). Here we develop and validate a CRISPR/Cas9 therapeutic strategy in fibroblasts isolated from SCA1 patients. We started from the screening of 10 different sgRNAs able to recognize regions upstream and downstream the CAG repeats, in exon 8 of ATXN1 gene. The two most promising sgRNAs, G3 and G8, whose efficiency was evaluated with an in vitro system, significantly downregulated the ATXN 1 protein expression. This downregulation was due to the introduction of indels mutations into the ATXN1 gene. Notably, with an RNA-seq analysis, we demonstrated minimal off-target effects of our sgRNAs. These preliminary results support CRISPR/Cas9 as a promising approach for treated polyQ-expanded diseases.

Mitochondrial impairment in patients with spinocerebellar ataxia type 3

2004 ◽  
Vol 31 (S 1) ◽  
Author(s):  
L Schöls ◽  
J Andrich ◽  
H Przuntek ◽  
K Müller ◽  
J Zange
Keyword(s):  
Spinocerebellar Ataxia ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 3 ◽  
Mitochondrial Impairment ◽  
Type 3
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