The Quebec Cooperative Study of Friedreich's Ataxia: 1974-1984 — 10 Years of Research

Barbeau, A.

doi:10.1017/s0317167100035228

Cited by 27 publications

(10 citation statements)

References 83 publications

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“…The dentate nucleus is the most severely affected region of the cerebellum in FRDA, and loss of myelinated fibres in the hilum of the dentate nucleus is prominent [31]. Ramos et al [32] showed cerebellar atrophy and increased area of the fourth ventricle in individuals with FRDA using CT scans and suggested these changes reflect atrophy of the dentate nucleus.…”

Section: Discussionmentioning

confidence: 99%

Superior Cerebellar Peduncle Atrophy in Friedreich’s Ataxia Correlates with Disease Symptoms

et al. 2010

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Friedreich's ataxia (FRDA) is the most common early onset inherited ataxia with clinical manifestations, including gradual progression of unremitting cerebellar-sensory ataxia, peripheral sensory loss, loss of lower limb tendon reflexes and hypertrophic cardiomyopathy. Although atrophy of the superior cerebellar peduncle (SCP) has been reported in several magnetic resonance imaging (MRI) studies of FRDA, the relationship of SCP changes to genetic and clinical features of FRDA has not been investigated. We acquired T1-weighted MRI scans in 12 right-handed individuals with FRDA, homozygous for a GAA expansion in intron 1 of FXN, as well as 13 healthy age-matched controls. The corrected cross-sectional areas of the right (left) SCP in the individuals with FRDA (R, 20 ± 7.9 mm(2); L, 25 ± 5.6 mm(2)) were significantly smaller than for controls (R, 68 ± 16 mm(2); L, 78 ± 17 mm(2)) (p < 0.001). The SCP volumes of individuals with FRDA were negatively correlated with Friedreich's ataxia rating scale score (r = -0.553) and disease duration (r = -0.541), and positively correlated with the age of onset (r = 0.548) (p < 0.05). These findings suggest that structural MR imaging of the SCP can provide a surrogate marker of disease severity in FRDA and support the potential role of structural MRI as a biomarker in the evaluation of neurodegenerative diseases and therapies.

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Section: Discussionmentioning

confidence: 99%

Superior Cerebellar Peduncle Atrophy in Friedreich’s Ataxia Correlates with Disease Symptoms

et al. 2010

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“…It is usually manifest, in its classical form, around puberty (1,2). At present, there is no clue to the basic biochemical defect in FA (3). Therefore, efforts to understand the disorder are directed towards isolating the disease gene on the basis of its genomic map position.…”

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confidence: 99%

Additional polymorphisms at marker loci D9S5 and D9S15 generate extended haplotypes in linkage disequilibrium with Friedreich ataxia.

Fujita

Hanauer

Sirugo

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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The gene for Friedreich ataxia (FA), a severe recessive neurodegenerative disease, has previously been shown to be tightly linked to the polymorphic markers D9S15 and D9S5 on human chromosome 9. In addition, the observation of linkage disequilibrium suggested that D9S15 is within 1 centimorgan (cM) of the disease locus, FRDA. Although D9SS did not show recombination with F-RDA, its localization was less precise (0-5 cM) due to its lower informativeness. We have now identified additional polymorphisms at both marker loci. Two cosmids spanning 50 kilobases around D9SS were isolated, and a probe derived from one of them detects an informative three-allele polymorphism. We have found a highly polymorphic microsatellite sequence at D9Sl5 which is rapidly typed by the DNA polymerase chain reaction. The polymorphism information contents at the D9S5 and D9S15 loci have been increased from 0.14 to 0.60 and from 0.33 to 0.74, respectively. between themselves in all informative meioses examined. The combination of our data with those published by Chamberlain et al. (6) showed that D9S15 is within one centimorgan (cM) ofthe disease locus (7). The linkage data, combined with physical mapping of D9S5 by in situ hybridization, support the assignment of FRDA to the proximal long arm of chromosome 9 (7). The very close proximity of D9S15 to FRDA was further indicated by the finding of a significant allelic association between FRDA and the Msp I restriction fragment length polymorphism (RFLP) at D9S15. In contrast, no linkage disequilibrium was noted between FRDA and previously described RFLPs at D9S5 (7). Several families in our initial linkage analysis were partially or completely uninformative, especially for D9SM. In an attempt to refine the genetic map around the FRDA locus and to further explore the linkage disequilibrium, a search has been conducted for new informative polymorphisms at the marker loci. We have isolated two overlapping cosmid clones which extend the D9S5 locus over 50 kilobases (kb). Additional RFLPs have been revealed by single-copy probes derived from these cosmids. One ofthese (probe 26P) detects a three-allele BstXI RFLP that increases considerably the heterozygosity of D9SM. We have also characterized within probe MCT112 (D9S15) a highly polymorphic "microsatellite" sequence (8,9). This allowed us to confirm that D9S5 and D9S15 are very tightly linked to FRDA. By using these polymorphisms at both loci, extended haplotypes can be generated, and some of them show highly significant linkage disequilibrium with FRDA. MATERIALS AND METHODSLinkage Studies. Forty-one FA families (34 from France), each with at least two affected children, were studied. Thirty-eight of these families have been previously analyzed for the Msp I RFLPs at D9S5 and D9S15 (7). All of these families conform to the diagnostic criteria for typical FA (1, 2). Southern blot analysis was performed as described (7). Linkage analysis was carried out by using the LINKAGE program (10) and the lod-1 support interval (lod = logl0 odds r...

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“…Although cardiomyopathy RECURRENT VT IN PATIENT WITH FRIEDREICH'S ATAXIA is typical of FA, it is not exclusive of disease and it may be that both ataxia and myocardiopathy are manifestations of a common pathogenic defect. 3 The main clinical cardiovascular manifestation is serious arrhythmia and complications related to the cardiomyopathy. 4,5 Cardiac arrhythmias may occur alone or in various combinations.…”

Section: Discussionmentioning

confidence: 99%

Recurrent Ventricular Tachycardia in Patient with Friedreich's Ataxia in the Absence of Clinical Myocardial Disease

Asaad

El‐Menyar

Suwaidi

2010

Pacing and Clinical Electrophysiology

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The Quebec Cooperative Study of Friedreich's Ataxia: 1974-1984 — 10 Years of Research

Cited by 27 publications

References 83 publications

Superior Cerebellar Peduncle Atrophy in Friedreich’s Ataxia Correlates with Disease Symptoms

Superior Cerebellar Peduncle Atrophy in Friedreich’s Ataxia Correlates with Disease Symptoms

Additional polymorphisms at marker loci D9S5 and D9S15 generate extended haplotypes in linkage disequilibrium with Friedreich ataxia.

Recurrent Ventricular Tachycardia in Patient with Friedreich's Ataxia in the Absence of Clinical Myocardial Disease

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