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.

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 Dystonia in Patients with Spinocerebellar Ataxia 3 - Machado-Joseph disease: An Underestimated Diagnosis?

2018 ◽  
Vol 12 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Ligia Maria Perrucci Catai ◽  
Carlos Henrique Ferreira Camargo ◽  
Adriana Moro ◽  
Gustavo Ribas ◽  
Salmo Raskin ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Movement Disorders ◽  
Disease Onset ◽  
Cag Repeat ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 3 ◽  
Generalized Dystonia ◽  
Machado Joseph Disease ◽  
Sca3 Patient ◽  
Type 3

Background:Spinocerebellar Ataxia type 3 (SCA3) or Machado-Joseph Disease (MJD) is characterized by cerebellar, central and peripheral symptoms, including movement disorders. Dystonia can be classified as hereditary and neurodegenerative when present in SCA3.Objective:The objective of this study was to evaluate the dystonia characteristics in patients with MJD.Method:We identified all SCA3 patients with dystonia from the SCA3 HC-UFPR database, between December 2015 and December 2016.Their medical records were reviewed to verify the diagnosis of dystonia and obtain demographic and clinical data. Standardized evaluation was carried out through the classification of Movement Disorders Society of 2013 and Burke Fahn-Marsden scale (BFM).Results:Amongst the presenting some common characteristics, 381 patients with SCA3, 14 (3.7%) subjects presented dystonia: 5 blepharospasm, 1 cervical dystonia, 3 oromandibular, 3 multifocal and 2 generalized dystonia. Regarding dystonia's subtypes, 71.4% had SCA3 subtype I and 28.6% SCA3 subtype II. The average age of the disease onset was 40±10.7 years; the SCA3 disease duration was 11.86± 6.13 years; the CAG repeat lengths ranged from 75 to 78, and the BFM scores ranged from 1.0 to 40. There was no correlation between the dystonia severity and CAG repeat lengths or the SCA3 clinical evolution.Conclusion:Dystonia in SCA3 is frequent and displays highly variable clinical profiles and severity grades. Dystonia is therefore a present symptom in SCA3, which may precede the SCA3 classic symptoms. Dystonia diagnosis is yet to be properly recognized within SCA3 patient.

scholarly journals Spinocerebellar ataxia type 6 in Brazil

2008 ◽  
Vol 66 (3b) ◽  
pp. 691-694 ◽  
Author(s):  
Hélio A.G. Teive ◽  
Renato Puppi Munhoz ◽  
Salmo Raskin ◽  
Lineu César Werneck
Keyword(s):  
Cerebellar Ataxia ◽  
Spinocerebellar Ataxia ◽  
Late Onset ◽  
Cag Repeat ◽  
Autosomal Dominant Cerebellar Ataxia ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 6 ◽  
Voltage Dependent ◽  
Pure Cerebellar Ataxia ◽  
Japanese Ancestry

Spinocerebellar ataxia type 6 (SCA 6) is an autosomal dominant cerebellar ataxia caused by CAG repeat expansion in the SCA6 gene, a alpha 1A voltage-dependent calcium channel subunit gene on chromosome 19p13. SCA-6 is characterized predominantly by slowly progressive pure cerebellar ataxia with late onset. We report three index patients, with pure, late onset, cerebellar ataxia, belonging to three different Brazilian families, all of them with Japanese ancestry, from Hokkaido island of Japan.

scholarly journals Polyglutamine-expanded ataxin-3: a target engagement marker for Spinocerebellar ataxia type 3 in peripheral blood

2021 ◽  
Author(s):  
Jeannette Huebener-Schmid ◽  
Kirsten Kuhlbrodt ◽  
Julien Peladan ◽  
Jennifer Faber ◽  
Magda M Santana ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Repeat Expansion ◽  
Cag Repeat ◽  
Spinocerebellar Ataxia Type ◽  
Clinical Parameters ◽  
Target Engagement ◽  
Spinocerebellar Ataxia Type 3 ◽  
Curative Therapy ◽  
Cag Repeat Expansion ◽  
Type 3

Abstract Spinocerebellar ataxia type 3 is a rare neurodegenerative disease, caused by a CAG repeat expansion leading to polyglutamine elongation in the ataxin-3 protein. While no curative therapy is yet available, preclinical gene silencing approaches to reduce polyglutamine-toxicity demonstrate promising results. In view of upcoming clinical trials, quantitative and easily accessible molecular markers are of critical importance as pharmacodynamic and particularly as target engagement markers. We developed a novel ultrasensitive immunoassay to measure specifically polyQ-expanded ataxin-3 in plasma and cerebrospinal fluid. Statistical analyses revealed a correlation with clinical parameters and a stability of polyglutamine-expanded ataxin-3 during conversion from the pre-ataxic to the ataxic phase.

scholarly journals Familial urothelial cell carcinoma of the bladder with autosomal dominant inheritance and late onset phenotype

SpringerPlus ◽  
2014 ◽  
Vol 3 (1) ◽  
pp. 281 ◽  
Author(s):  
Robin Brown ◽  
Deirdre E Donnelly ◽  
Derek Allen ◽  
Maurice B Loughrey ◽  
Patrick J Morrison
Keyword(s):  
Cell Carcinoma ◽  
Autosomal Dominant ◽  
Late Onset ◽  
Urothelial Cell ◽  
Autosomal Dominant Inheritance ◽  
Urothelial Cell Carcinoma ◽  
Dominant Inheritance ◽  
Carcinoma Of The Bladder

scholarly journals CAG repeat length does not associate with the rate of cerebellar degeneration in spinocerebellar ataxia type 3

2017 ◽  
Vol 13 ◽  
pp. 97-105 ◽  
Author(s):  
Shang-Ran Huang ◽  
Yu-Te Wu ◽  
Chii-Wen Jao ◽  
Bing-Wen Soong ◽  
Jiing-Feng Lirng ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Cerebellar Degeneration ◽  
Repeat Length ◽  
Cag Repeat ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 3 ◽  
Type 3

scholarly journals DNAzyme Cleavage of CAG Repeat RNA in Polyglutamine Diseases

2021 ◽  
Author(s):  
Nan Zhang ◽  
Brittani Bewick ◽  
Jason Schultz ◽  
Anjana Tiwari ◽  
Robert Krencik ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Cag Repeat ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 3 ◽  
Therapeutic Value ◽  
Expanded Allele ◽  
Allele Specific ◽  
Aggresome Formation ◽  
Polyq Diseases ◽  
Type 3

AbstractCAG repeat expansion is the genetic cause of nine incurable polyglutamine (polyQ) diseases with neurodegenerative features. Silencing repeat RNA holds great therapeutic value. Here, we developed a repeat-based RNA-cleaving DNAzyme that catalyzes the destruction of expanded CAG repeat RNA of six polyQ diseases with high potency. DNAzyme preferentially cleaved the expanded allele in spinocerebellar ataxia type 1 (SCA1) cells. While cleavage was non-allele-specific for spinocerebellar ataxia type 3 (SCA3) cells, treatment of DNAzyme leads to improved cell viability without affecting mitochondrial metabolism or p62-dependent aggresome formation. DNAzyme appears to be stable in mouse brain for at least 1 month, and an intermediate dosage of DNAzyme in a SCA3 mouse model leads to a significant reduction of high molecular weight ATXN3 proteins. Our data suggest that DNAzyme is an effective RNA silencing molecule for potential treatment of multiple polyQ diseases.

scholarly journals Diagnostic Challenges Posed by Preceding Peripheral Neuropathy in Very Late-onset Spinocerebellar Ataxia Type 3

2019 ◽  
Vol 58 (1) ◽  
pp. 119-122
Author(s):  
Atsuhiko Sugiyama ◽  
Yukari Sekiguchi ◽  
Minako Beppu ◽  
Takayuki Ishige ◽  
Kazuyuki Matsushita ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Spinocerebellar Ataxia ◽  
Late Onset ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 3 ◽  
Type 3

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.

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