PURPOSE: Polyglutamine diseases are a group of diseases caused by the expansion of a polyglutamine tract in the protein. The present study was performed to verify if polyglutamine disease transgenic Drosophila models show similar dysfunctions as are seen in human patients. METHODS: Polyglutamine disease transgenic Drosophila were tested for their climbing ability. And using genetic methods, the effects of anti-apoptotic gene bcl-2 and chemical chaperones on neurodegeneration were observed. Also, spinocerebellar ataxia 2 (SCA2) transgenic Drosophila lines were generated for future studies. RESULTS: Expanded forms of spinocerebellar ataxia 3 (SCA3) transgenic protein causes characteristic locomotor dysfunction when expressed in the nervous system of Drosophila but the anti-apoptotic gene bcl-2 shows no evidence of ameliorating the deleterious effect of the expanded protein. However, Glycerol, a chemical chaperone, seemed to reduce the toxicity, at least in the eyes of the transgenic flies. The level SCA2 expression is too weak in the transgenic SCA2 Drosophila for evaluation. CONCLUSION: SCA3 transgenic Drosophila show ataxic behavior as observed in human patients. Chemical chaperones such as glycerol may prove beneficial in this class of genetic disease, which has no current method of cure.
Diptera ; Drosophila* ; Glycerol ; Humans ; Machado-Joseph Disease ; Nervous System ; Spinocerebellar Ataxias

The genetic locus of spinocerebellar ataxia type 3 (SCA3) is linked to chromosome 14q 24.3-qter like Machado-Joseph disease (MJD). The number of CAG repeats on mutant chromosome correlates positively with severity of disease, and negatively with the age of onset. However, the interindividual variation cannot be explained solely by the size of CAG repeats. We experienced a patient of juvenile onset SCA3, who had a relatively small length of CAG repeats. Several factors may have contributed in determining the age of on set in our case. The normal allele or modifying gene at other loci may have relationship with the age of onset and phenotype. Also, it should be considered that size of the expanded repeat in lymphocyte could be different from the size in cells of involved structures.
Age of Onset ; Alleles ; Genetic Loci ; Humans ; Lymphocytes ; Machado-Joseph Disease* ; Phenotype ; Spinocerebellar Ataxias* ; Trinucleotide Repeats

OBJECTIVE: Machado-Joseph disease (MJD) is a spinocerebellar ataxia, and osteoporosis is a multifactor disease that may affect patients with neurologic conditions. The frequency of osteoporosis among MJD patients, however, has not been studied. The purpose of this study is to evaluate bone mineral density (BMD) and identify correlations between clinical factors and frequency of vertebral fractures in patients with MJD. METHODS: Clinical data, lumbar X-rays and BMD data were obtained in 30 patients with MJD. RESULTS: Ten patients (33.3%) showed low BMD in at least one of the sites studied based on Z-scores. The Z-score correlated directly with body mass index, and the femoral neck Z-score was inversely correlated with cytosine-adenine-guanine (CAG) expansion. There was no correlation between BMD and other clinical factors. Forty-three percent of the patients reported previous pathologic fractures. Five patients (16.7%) had at least one fracture detected by lumbar X-ray. CONCLUSION: Low BMD and fractures are frequent among MJD patients, and careful management of BMD may be beneficial for these patients.
Body Mass Index ; Bone Density ; Femur Neck ; Fractures, Spontaneous ; Humans ; Machado-Joseph Disease ; Osteoporosis ; Spinocerebellar Ataxias

No abstract available.
Spinocerebellar Ataxias

No abstract available.
Spinocerebellar Ataxias* ; Trinucleotide Repeats

BACKGROUNDSpinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders that primarily cause the degeneration in the cerebellum, spinal cord, and brainstem. We study the clinical characteristics, radiological features and gene mutation in Chinese families with SCAs.

METHODSIn this study, we investigated 10 SCAs Chinese families with SCA1, SCA3/Machado-Joseph disease (MJD), SCA7, SCA8. There were 27 people who were genetically diagnosed as SCA, of which 21 people showed clinical symptoms, and 6 people had no clinical phenotype that we called them presymptomatic patients. In addition, 3 people with cerebellar ataxia and cataracts were diagnosed according to the Harding diagnostic criteria but failed to be recognized as SCAs on genetic testing. Clinical characteristic analyses of each type of SCAs and radiological examinations were performed.

RESULTSWe found that SCA3/MJD was the most common subtype in Han population in China, and the ratio of the pontine tegmentum and the posterior fossa area was negatively correlated with the number of cytosine-adenine-guanine (CAG) repeats; the disease duration was positively correlated with the International Cooperative Ataxia Rating Scale score; and the CAG repeats number of abnormal alleles was negatively correlated with the age of onset.

CONCLUSIONSCollectively our study is a systematic research on SCAs in China, which may help for the clinical diagnosis and prenatal screening of this disease, and it may also aid toward better understanding of this disease.

Adult ; DNA Repeat Expansion ; genetics ; Female ; Humans ; Machado-Joseph Disease ; genetics ; pathology ; Male ; Mutation ; genetics ; Spinocerebellar Ataxias ; genetics ; pathology ; Trinucleotide Repeat Expansion ; genetics

The spinocerebellar ataxia are a heterogeneous group of neurodegeneative disorders varying in both clinical manifestations and mode of inheritance. Recently, CAG trinucleotide repeats have been identified in inherited neurodegenerative disease such as dentrorubopallidoluysian atrophy, spinocerebellar ataxia type 1 (SCA1), Machado-Joseph disease (MJD) and SCA3. Individuals with SCA3 are phenotypically similar to those with SCA1 and, like MJD, the locus is linked to genetic markers on chromosome 14q24.3-qter. We experienced 38 year old man who presented with slowly progressive cerebellar dysfunction. Family history was not remarkable. We could not observe orofacial fasciculation, ophthalmoplegia, optic atrophy, peripheral neuropathy, amyotrophy, or dystonia. We peformed genomic polymerase chain reaction (PCR) analysis with patient's blood samples using the following primers: MJD52 (5'-CCAGTGAC TACTTTGATTCG-3') and MJD25 (3'-AAGTGTAGGTACACTTTCCGGT-5'). We found that his gene contained expanded CAG repeats (CAG repeat number was 69). We reported a clinically suspected sporadic case of genetically confirmed SCA3 who shared a similar genetic mutation with MJD and similar clinical presentation with SCA1. To our knowledge, this is the first case report on SCA3 in Korea. We think that the further genetic study with his family members should be done to evaluate mode of inheritance in this case.
Adult ; Ataxia ; Cerebellar Diseases ; Dystonia ; Fasciculation ; Genetic Markers ; Humans ; Korea ; Machado-Joseph Disease* ; Neurodegenerative Diseases ; Ophthalmoplegia ; Optic Atrophy ; Peripheral Nervous System Diseases ; Polymerase Chain Reaction ; Spinocerebellar Ataxias* ; Trinucleotide Repeats ; Wills*

No abstract available.
Ataxia* ; Atrophy* ; Cerebellar Ataxia ; Spinocerebellar Ataxias*

Child ; Humans ; Male ; Spinocerebellar Ataxias ; diagnosis

OBJECTIVETo investigate the normal range of (CAG)n in spinocerebellar ataxia type 1 (SCA1) gene and spinocerebellar ataxia type 3 (SCA3/MJD) gene in 110 normal subjects of Han population in Northeastern China, to assess the genotypes for clinically diagnosed spinocerebellar ataxia(SCA) individuals including 25 patients from 8 families and 6 sporadic patients, and to make presymptomatic and prenatal diagnosis.

METHODSDNA fragments from the normal subjects and the patients were detected by fluorescence-PCR. Homozygosities were selected for DNA sequencing.

RESULTSThe normal ranges of (CAG)n of SCA1 and SCA3/MJD were 20-39 and 14-38 repeats respectively, SCA1 was found mostly to be 26 and 27 repeats, allele frequency 34.09% and 20.91%; heterozygosity was 84.55%, SCA3/MJD was found mostly to be 14 repeats, allele frequency 39.55%, heterozygosity was 78.18%.(CAG)(68) of SCA3/MJD gene of one affected individual had been found in a family but no CAG mutative expansion in related members was observed.

CONCLUSIONThe normal ranges of CAG repeats vary with areas and races. SCAs genotyping is the first choice in presymptomatic and prenatal diagnosis.

Ataxin-1 ; Ataxin-3 ; Ataxins ; China ; DNA ; chemistry ; genetics ; Family Health ; Female ; Gene Frequency ; Genotype ; Humans ; Machado-Joseph Disease ; diagnosis ; genetics ; Male ; Nerve Tissue Proteins ; genetics ; Nuclear Proteins ; genetics ; Pedigree ; Repressor Proteins ; Sequence Analysis, DNA ; Spinocerebellar Ataxias ; diagnosis ; genetics ; Trinucleotide Repeat Expansion ; genetics ; Trinucleotide Repeats ; genetics