Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007758 (cerebellar ataxia)
 3,609 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Friedreich's ataxia is an autosomal recessively inherited neurodegenerative disorder caused by expansions of an unstable GAA trinucleotide repeat in the STM7/X25 gene on chromosome 9q. We studied the (GAA)n polymorphism in 178 healthy controls and 102 patients with idiopathic ataxia. The repeat size ranged from 7 to 29 (GAA)n motifs on normal chromosomes and from 66 to 1360 trinucleotide repetitions in Friedreich's ataxia patients. Meiotic instability of expanded alleles was observed without significant differences in maternal and paternal transmissions. Thirty-six of 102 patients were typed homozygous for expanded (GAA)n alleles. Twenty-seven of these presented with the typical Friedreich's ataxia symptoms and nine patients with an atypical Friedreich's ataxia phenotype. Before molecular genetic diagnosis had been performed seven of these patients had been classified as early onset cerebellar ataxia and two as idiopathic sporadic cerebellar ataxia of late onset. In contrast, in one family with typical Friedreich's ataxia phenotype we did not find an expanded allele; this suggests that there can be either point mutations in the X25 gene on both chromosomes or locus heterogeneity in Friedreich's ataxia. The phenotypic spectrum of Friedreich's ataxia is much broader than considered before. Early onset, areflexia, extensor plantar responses and reduced vibration sense should no longer be considered essential diagnostic criteria of Friedreich's ataxia. In comparison with the non-Friedreich's ataxia group hypertrophic cardiomyopathy seems to be the only symptom specific for Friedreich's ataxia. However, it is not obligatory. The phenotype is significantly influenced by the number of GAA repeats with close genotype-phenotype relationships when the smaller of the two alleles is considered. Repeat length correlated inversely with age at onset, onset of dysarthria and progression rate. In conclusion, molecular genetic analysis appears mandatory for the diagnosis and genetic counselling of Friedreich's ataxia. The molecular genetic test should be applied not only to patients with typical Friedreich's ataxia phenotype but also in all cases of idiopathic autosomal recessive or sporadic ataxia.
 ...
PMID:Friedreich's ataxia. Revision of the phenotype according to molecular genetics. 944 68

The aim of the present study was (i) to compare disease progression and survival in different types of degenerative ataxia, and (ii) to identify variables that may modify the rate of disease progression. We included patients suffering from Friedreich's ataxia (FRDA, n = 83), early onset cerebellar ataxia (EOCA, n = 30), autosomal dominant cerebellar ataxia (ADCA) type I (ADCA-I, n = 273), ADCA-III (n = 13) and multiple system atrophy (MSA, n = 67). Molecular genetic testing allowed us to assign 202 ADCA-I patients to one of the following subgroups: spinocerebellar ataxia type I (SCAI, n = 36), SCA2 (n = 56) and SCA3 (n = 110). To assess disease progression we defined the following disease stages: stage 0 = no gait difficulties; stage 1 = disease onset, as defined by onset of gait difficulties; stage 2 = loss of independent gait; stage 3 = confinement to wheelchair; stage 4 = death. Disease progression was most rapid in MSA, intermediate in FRDA, ADCA-I and ADCA-III and slowest in EOCA. The rate of progression was similar in SCA1, SCA2 and SCA3. The CAG repeat length was a significant risk factor for faster progression in SCA2 and SCA3, but not in SCA1. In FRDA, the time until confinement to wheelchair was shorter in patients with earlier disease onset, suggesting that patients with long GAA repeats and early disease onset have a poor prognosis. Female gender increased the risk of becoming dependent on walking aids or a wheelchair, but it did not influence survival in FRDA, SCA3 and MSA. In SCA2, female gender was associated with shortened survival. In MSA, later age of onset increased the risk of rapid progression and death.
 ...
PMID:The natural history of degenerative ataxia: a retrospective study in 466 patients. 957 87

Unstable (CAG)n trinucleotide repeat microsatellites are hypothesized to cause schizophrenia. The (CAG)n microsatellite of dominant spinal cerebellar ataxia type 1 (SCA1) is a candidate schizophrenia gene. Autism results from expansions of (CGG)n and (GAA)n trinucleotide repeat stretches at fragile X syndrome (FRAXA), and the recessive Friedreich's ataxia (FA). Dominant ataxia genes may cause schizophrenia and recessive ataxia genes may cause autism. Syndromes with autism show purine synthesis defects (PSDs) and/or pigmentation defects (PDs). Autism is caused by very lengthy expansions of (CAG)n, (CGG)n and (GAA)n repeats, while schizophrenia results from much smaller (CAG)n and (CGG)n repeat expansions.
 ...
PMID:Expanded (CAG)n, (CGG)n and (GAA)n trinucleotide repeat microsatellites, and mutant purine synthesis and pigmentation genes cause schizophrenia and autism. 979

Friedreich's ataxia is the most common inherited ataxia. Ninety-six percent of patients are homozygous for GAA trinucleotide repeat expansions in the first intron of the frataxin gene. The remaining cases are compound heterozygotes for a GAA expansion and a frataxin point mutation. We report here the identification of 10 novel frataxin point mutations, and the detection of a previously described mutation (G130V) in two additional families. Most truncating mutations were in exon 1. All missense mutations were in the last three exons coding for the mature frataxin protein. The clinical features of 25 patients with identified frataxin point mutations were compared with those of 196 patients homozygous for the GAA expansion. A similar phenotype resulted from truncating mutations and from missense mutations in the carboxy-terminal half of mature frataxin, suggesting that they cause a comparable loss of function. In contrast, the only two missense mutations located in the amino-terminal half of mature frataxin (D122Y and G130V) cause an atypical and milder clinical presentation (early-onset spastic gait with slow disease progression, absence of dysarthria, retained or brisk tendon reflexes, and mild or no cerebellar ataxia), suggesting that they only partially affect frataxin function. The incidence of optic disk pallor was higher in compound heterozygotes than in expansion homozygotes, which might correlate with a very low residual level of normal frataxin produced from the expanded allele.
 ...
PMID:Friedreich's ataxia: point mutations and clinical presentation of compound heterozygotes. 998 22

The aim of this study was to determine phenotypie characteristics of patients with early onset cerebellar ataxia (EOCA) with preserved tendon reflexes. The series comprises 25 patients, representing 10% of all ataxic patients who have been genetically studied in our laboratory since 1990. There were 11 males and 14 females. Fourteen patients were homozygous for the GAA expansion on chromosome 9q13 (group 1) and therefore a diagnosis of Friedreich's ataxia with retained reflexes (FARR) was given. The remaining 11 patients had two normal non-expanded alleles (group 2) and a working diagnosis of EOCA with retained reflexes (EOCARR) was established. Mean ages of onset were 13.7 +/- 5.9 years (3-25) for group 1 and 10.3 +/- 7.3 for group 2; the difference was not significant. Frequencies of symptoms and signs were also comparable for both groups the only significant differences being the higher frequency of nystagmus, cardiomyopathy and sensory neuropathy in group 1 patients. There was a tendency for FARR patients to have higher frequencies of hypopallesthesia in the lower limbs and skeletal deformities. In none of the cases diabetes mellitus was observed. We conclude that differentiation of FARR and EOCARR may be suspected by classical clinical and electrophysiological data and confirmed by analysis of the GAA repeat.
 ...
PMID:Early onset cerebellar ataxia and preservation of tendon reflexes: clinical phenotypes associated with GAA trinucleotide repeat expanded and non-expanded genotypes. 1019 66

Friedreich ataxia (FRDA), the most common autosomal recessive ataxia, is caused in 94% of cases by homozygous expansions of an unstable GAA repeat localised in intron 1 of the X25 gene. We have investigated this mutation in five Brazilian patients: four with typical FRDA findings and one patient with atypical manifestations, who was considered to have some other form of cerebellar ataxia with retained reflexes. The GAA expansion was detected in all these patients. The confirmation of FRDA diagnosis in the atypical case may be pointing out, as in other reports, that clinical spectrum of Friedreich's ataxia is broader than previously recognised and includes cases with intact tendon reflexes.
 ...
PMID:Clinical and molecular studies in five Brazilian cases of Friedreich ataxia. 1034 15

Early onset cerebellar ataxia with retained tendon reflexes (EOCA) is a clinical syndrome characterised by progressive cerebellar ataxia with an onset before the age of 25 years and a wide spectrum of associated features. It is distinguished from Friedreich's ataxia (FA) mainly by the preservation of tendon reflexes, a better prognosis, and the absence of GAA expansion in the frataxin gene. Although EOCA is thought to be a hereditary disorder with an autosomal recessive mode of inheritance, genetic heterogeneity might underlie the spectrum of clinical features. In this case report we describe a patient with EOCA accompanied by pes cavus, hammer toes and peripheral neuropathy. The patient's father did not have any ataxia, but had the same foot deformities as his daughter and a slight peripheral neuropathy. The possible relationship between these clinical features is discussed.
 ...
PMID:Early onset cerebellar ataxia with retained tendon reflexes: foot deformity in a first grade family member. 1062 55

We present here 5 patients with hereditary cerebellar ataxia with peripheral neuropathy and mental retardation as determined by clinical, pathological, and molecular studies. The most characteristic features of this disorder, in contrast to Friedreich's ataxia, were early onset of ataxic gait, mental retardation, and a marked atrophy of the cerebellum. Sural nerve biopsy showed a reduction of myelinated fibers. The expansion of a GAA triplet repeat within the first intron of the frataxin gene, which causes Friedreich's ataxia, was not identified in any of the patients. Hereditary cerebellar ataxia with peripheral neuropathy and mental retardation represents a specific clinical entity that so far has only been described in Japan.
 ...
PMID:Hereditary cerebellar ataxia with peripheral neuropathy and mental retardation. 1068 65

This study aimed to determine if cerebellar ataxia, hypogonadism and chorioretinopathy (AHCR) is associated with mutations in mitochondrial DNA or in genes responsible for spinocerebellar ataxias (SCA1, SCA2, SCA3 and Friedreich's ataxia). Two brothers with cerebellar ataxia, hypogonadism and chorioretinopathy and their unaffected parents underwent molecular analysis for duplications and deletions in mitochondrial DNA (mtDNA), point mutations in the ATP ase 6 gene, and expansions of CAG repeats (at 6p22-p23, 12q24.1, 14q32.1) and of GAA repeats (at gene X25 on chromosome 9q13). The research was negative for all mutations. Our findings confirm that AHCR is a distinct disease within the inherited cerebellar ataxias.
 ...
PMID:Cerebellar ataxia, hypogonadism and chorioretinopathy: molecular analysis of an Italian family. 1093 59

Disease-causing mutations have been identified in various entities of autosomal dominant ataxia and in Friedreich's ataxia. However, no molecular pathogenic factor is known to cause idiopathic cerebellar ataxias. We investigated the CAG/CTG trinucleotide repeats causing spinocerebellar ataxia types 1, 2, 3, 6, 7, 8 and 12, and the GAA repeat of the frataxin gene in 124 patients apparently suffering from idiopathic sporadic ataxia, including 20 patients with the clinical diagnosis of multiple system atrophy. Patients with a positive family history, a typical Friedreich phenotype, or symptomatic ataxia were excluded. Genetic analyses uncovered the most common Friedreich mutation in 10 patients with an age at onset between 13 and 36 years. The SCA6 mutation was present in nine patients with disease onset between 47 and 68 years of age. The CTG repeat associated with SCA8 was expanded in three patients. One patient had SCA2 attributable to a de novo mutation from a paternally transmitted, intermediate allele. We did not identify the SCA1, SCA3, SCA7 or SCA12 mutation in idiopathic sporadic ataxia patients. No trinucleotide repeat expansion was detected in the MSA subgroup. This study has revealed the genetic basis in 19% of apparently idiopathic ataxia patients. SCA6 is the most frequent mutation in late onset cerebellar ataxia. The frataxin trinucleotide expansion should be investigated in all sporadic ataxia patients with onset before age 40, even when the phenotype is atypical for Friedreich's ataxia.
 ...
PMID:Genetic background of apparently idiopathic sporadic cerebellar ataxia. 1103 Apr 10


1 2 3 Next >>