Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autosomal dominant cerebellar ataxias (ADCA) are a clinically heterogeneous group of neurodegenerative disorders caused by unstable CAG repeat expansions encoding polyglutamine tracts. Five spinocerebellar ataxia genes (SCA1, SCA2, SCA3, SCA6 and SCA7) and another related dominant ataxia gene (DRPLA) have been cloned, allowing the genetic classification of these disorders. We present here the molecular analysis of 87 unrelated familial and 60 sporadic Spanish cases of spinocerebellar ataxia. For ADCA cases 15% were SCA2, 15% SCA3, 6% SCA1, 3% SCA7, 1% SCA6 and 1% DRPLA, an extremely rare mutation in Caucasoid populations. About 58% of ADCA cases remained genetically unclassified. All the SCA1 cases belong to the same geographical area and share a common haplotype for the SCA1 mutation. The expanded alleles ranged from 41 to 59 repeats for SCA1, 35 to 46 [corrected] for SCA2, 67 to 77 for SCA3, and 38 to 113 for SCA7. One SCA6 case had 25 repeats and one DRPLA case had 63 repeats. The highest CAG repeat variation in meiotic transmission of expanded alleles was detected in SCA7, this being of +67 units in one paternal transmission and giving rise to a 113 CAG repeat allele in a patient who died at 3 years of age. Meiotic transmissions have also shown a tendency to more frequent paternal transmission of expanded alleles in SCA1 and maternal in SCA7. All SCA1 and SCA2 expanded alleles analyzed consisted of pure CAG repeats, whereas normal alleles were interrupted by 1-2 CAT trinucleotides in SCA1, except for three alleles of 6, 14 and 21 CAG repeats, and by 1-3 CAA trinucleotides in SCA2. No SCA or DRPLA mutations were detected in the 60 sporadic cases of spinocerebellar ataxia, but one late onset patient was identified as a recessive form due to GAA-repeat expansions in the Friedreich's ataxia gene.
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PMID:Spinocerebellar ataxias in Spanish patients: genetic analysis of familial and sporadic cases. The Ataxia Study Group. 1045 42

We evaluated the prevalence of the SCA2 mutation among 224 Italian patients affected by typical Parkinsonism, including 145 sporadic and 79 familial forms. Pink1, Parkin, and LRRK2 gene mutations had been excluded previously. Molecular testing for the CAG expansion at the SCA 2 locus was performed on leukocyte DNA. Cloning and sequencing of the expanded allele was performed in patients positive for the SCA2 expansion. A 38 CAG expansion was detected in 1 of 79 families studied. The proband, a male age 67, and his sister, age 69, were both affected by a benign form of L-dopa-responsive Parkinsonism not associated with cerebellar signs. The inheritance was autosomal dominant. The CAG expansion was stable through meiotic transmission: sequence analysis showed that the CAG stretch was interrupted by 3 CAA. Our study shows that CAG expansion at the SCA 2 locus may represent a genetic cause of familial L-dopa-responsive Parkinsonism among Italian patients. The stability of the pathological CAG expansion detected in this family was related to the presence of CAA interruptions. These findings, together with literature data, suggest that the molecular intrinsic structure of the expanded allele may modulate the phenotypic expression of the SCA2 mutation.
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PMID:Prevalence of spinocerebellar ataxia type 2 mutation among Italian Parkinsonian patients. 1714 20

The objective of this study was to determine the prevalence of hereditary ataxias in Cuba, with a special focus on the clinical and molecular features of SCA2. Clinical assessments were performed by neurological examinations and application of the SARA scale. Molecular analyses of genes SCA1-3, SCA6, SCA17 and DRPLA identified 753 patients with SCA and 7173 asymptomatic relatives, belonging to 200 unrelated families. 86.79% of all SCA patients were affected with SCA2. In the Holguin province, the average population prevalence of SCA2 is 40.18x10(5) inhabitants, with the remarkable figure of 141.66x10(5) in the Baguanos municipality. The high prevalence of the SCA2 mutation in Holguin reflects most likely a founder effect. The stabilization of the prevalence along time suggests the existence of premutated chromosomes with pure CAG, acting as reservoir for further expansions. CAG repeat length correlated inversely with age at onset, accounting for 80% of the variability. Genetic anticipation was observed in the 80% of transmissions. Repeat instability was greater in paternal transmissions whereas CAG expansions without anticipation was observed in 10.97% suggesting the effect of CAA interruptions in the CAG segment, which decrease the toxicity of the abnormal ataxin-2, and/or other protective factors.
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PMID:Molecular epidemiology of spinocerebellar ataxias in Cuba: insights into SCA2 founder effect in Holguin. 1942 75

It has recently been suggested that short expansions of CAG repeat in the gene ATXN-2 causing SCA2 (spinocerebellar ataxia type 2) are associated with an increased risk of amyotrophic lateral sclerosis (ALS) in the populations of the USA and northern Europe. In this study, we investigated the role of ATXN-2 in Italian patients clinically diagnosed with ALS and characterized the molecular structure of ATXN-2 expansions. We assessed the size of the CAG repeat in ATXN-2 exon 1 in 232 Italian ALS patients and 395 matched controls. ATXN-2 expanded alleles containing > 30 repeats have been observed in seven sporadic ALS patients (3.0%), while being absent in the controls (p = 0.00089). Four out of the seven patients had an ATXN-2 allele in the intermediate-fully pathological range: one with 32 repeats, 2 with 33 repeats and 1 with 37 repeats, accounting for 1.7% of the ALS cohort. Sequencing of expanded (> 32) alleles showed that they were all interrupted with at least one CAA triplet. ATXN-2 alleles with the same length and structure have been reported in SCA2 patients with parkinsonism or in familial and sporadic Parkinson. Conversely, the phenotype of the present patients was typically ALS with no signs or symptoms of ataxia or parkinsonism. In conclusion, the findings of ATXN-2 expansions in pure ALS cases suggest that ALS may be a third phenotype (alongside ataxia/parkinsonism and pure Parkinson) associated with ATXN-2 interrupted alleles.
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PMID:ATXN-2 CAG repeat expansions are interrupted in ALS patients. 2153 50

The spinocerebellar ataxias (SCA) are a genetically and clinically heterogeneous group of diseases, characterized by dominant inheritance, progressive cerebellar ataxia and diverse extracerebellar symptoms. A subgroup of the ataxias is caused by unstable CAG-repeat expansions in their respective genes leading to pathogenic expansions of polyglutamine stretches in the encoded proteins. In general, unstable CAG repeats have an uninterrupted CAG repeat, whereas stable CAG repeats are either short or interrupted by CAA codons, which - like CAG codons - code for glutamine. Here we report on an infantile SCA2 patient who, due to germ-line CAG repeat instability in her father, inherited an extremely expanded CAG repeat in the SCA2 locus. Surprisingly, the expanded allele of the father was an interrupted CAG repeat sequence. Furthermore, analyses of single spermatozoa showed a high frequency of paternal germ-line repeat sequence instability of the expanded SCA2 locus.
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PMID:Germ-line CAG repeat instability causes extreme CAG repeat expansion with infantile-onset spinocerebellar ataxia type 2. 2304 44