Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There have been three reports since 1969 of members of a "W" family with autosomal dominant spinocerebellar ataxia (SCA), and various conclusions have been drawn about the nosology. This pedigree has been traced back over 300 years through 11 generations. Although phenotypically similar to the disorder in the Schut-Swier, Nino, and other kindreds, the disorder in the W family is not linked to the SCA1 locus on chromosome 6, as reported in those hereditary ataxia pedigrees. The W family represents the largest such North American kindred yet reported. We examined 33 family members of a distantly related branch of the W family, determined the cumulative age of onset, and projected the number of present-day gene carriers. Two cases illustrate the spectrum of symptoms among family members. Age of onset and presenting symptom, however, seem to correlate both in our patients and in those previously reported. Between 2,000 and 5,000 individuals are estimated to be at risk of developing the disorder within this pedigree alone. The pedigree reported here will be valuable in the identification and cloning of a gene for hereditary ataxia, designated "SCA2" at the Eleventh International Workshop on Human Gene Mapping.
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PMID:A 17th-century founder gives rise to a large north American pedigree of autosomal dominant spinocerebellar ataxia not linked to the SCA1 locus on chromosome 6. 143 21

Hereditary spinocerebellar ataxia (SCA) is a relatively common disorder in the Western Cape region of South Africa. At present there are no genetic markers available for prenatal or presymptomatic diagnosis. A large kindred of mixed ancestry with late onset SCA was studied in which the disorder segregated in an autosomal dominant fashion. HLA typing was undertaken on 44 family members, and the HLA haplotypes were assigned on the basis of segregation. The LIPED computer program, with a correction factor allowing for the age of onset, was used to analyze the pedigree for linkage to HLA. Of 22 individuals in whom disease status could be definitely assessed, only one recombinant between HLA and the SCA locus occurred. The lod score reached a maximum of 4.13 at a recombination fraction of 0.05, indicating the odds to be approximately 13,500 to 1 in favor of linkage between HLA and the putative disease allele for SCA. A possible recombination within the HLA region suggested that the disease allele lies telomeric of the HLA region. In view of the recent demonstration of tight linkage between SCA1 and D6S89, however, HLA should not be used for presymptomatic diagnosis or genetic counselling.
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PMID:Adult onset spinocerebellar ataxia linked to HLA in a South African kindred of mixed ancestry. 144 May 65

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative spinocerebellar ataxia that has been described primarily in families of Azorean or Portuguese descent. MJD and chromosome 6p-linked spinocerebellar ataxia (SCA1) are difficult to differentiate clinically, and it has been suggested that they may be allelic variants of the same disorder. We have tested MJD families for linkage to six DNA sequence polymorphisms located on chromosome 6p, including the highly informative dinucleotide repeat, D6S89. Seventeen centimorgans telomeric to and 41 cM centromeric to D6S89, a region that includes the SCA1 locus reported to be within 3 cM of D6S89, have been excluded. These data provide conclusive evidence that MJD and SCA1 are nonallelic.
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PMID:The Machado-Joseph disease locus is different from the spinocerebellar ataxia locus (SCA1). 163 14

Two large Italian pedigrees with HLA-linked spinocerebellar ataxia (SCA1) were typed for HLA-A, -B and -DR as well as for markers either distal (F13A, D6S8) or proximal (D6S29, GLO1) to HLA. Pairwise linkage analyses of SCA1 vs. HLA-A, -B, and -DR showed peak lodscores of 5.3, 5.6 and 3.3 respectively at 7% recombination. Negative lodscores significantly excluded linkage with F13A at less than 5% and with GLO1 at less than 10%. The lodscores with D6S8 and D6S29 had only low peaks. Recombination events in the two pedigrees and the estimated genetic distances of SCA1 from GLO1 and HLA favour the hypothesis of a SCA1 location distal to both of them. An order cen-GLO1-HLA-SCA1-tel appears therefore most likely with present data. These results are discussed in relation to previous reports placing SCA1 distal to HLA in two families and
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PMID:Spinocerebellar ataxia (SCA1) in two large Italian kindreds: evidence in favour of a locus position distal to GLO1 and the HLA cluster. 167 45

Two large kindreds with HLA-linked, autosomal dominant spinocerebellar ataxia (SCA1) were examined with markers from chromosome 6p to determine the location of the SCA1 locus. Results of the three-point analysis between the markers HLA-A, SCA1, and F13A overwhelmingly favor the conclusion that SCA1 is located distal of HLA and proximal of F13A. In addition, our data strongly support the conclusion that SCA1 lies centromeric and genetically very close to the highly informative D6S89 marker within the 8-cM chromosomal segment flanked by the D6S88 and D6S89 markers. In the two kindreds, one recombinant was observed between D6S89 and SCA1, resulting in a recombination fraction of .014 between the two loci.
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PMID:Localization of the autosomal dominant HLA-linked spinocerebellar ataxia (SCA1) locus, in two kindreds, within an 8-cM subregion of chromosome 6p. 167 61

SCA1 is an adult-onset autosomal dominant ataxia that is genetically linked to loci on chromosome 6p. A highly informative GT-repeat marker, D6S89, has been closely linked to the SCA1 locus in five large kindreds. We have used this marker to perform linkage analysis in a smaller autosomal dominant ataxia family consisting of five generations designated as the Nebraska kindred. This kindred includes 33 affected (12 living) and 40 first-generation at-risk individuals. We examined eight affected individuals; all had gait and limb ataxia. We analyzed the D6S89 locus by the polymerase chain reaction. Based on the analysis of 31 individuals from this kindred, we statistically excluded linkage to D6S89 for moderate-to-tight linkage (less than 11% recombination). These data clearly demonstrate genetic heterogeneity among the autosomal dominant ataxias. In addition, we obtained linkage data for HLA-A and SCA1 in this kindred. Comparison of HLA-A with D6S89 shows the latter marker to be more powerful. Use of D6S89 and other highly polymorphic markers in this region will greatly facilitate genetic classification of ataxias and make presymptomatic diagnosis of SCA1 feasible.
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PMID:Autosomal dominant spinocerebellar ataxia: locus heterogeneity in a Nebraska kindred. 173 63

A locus for an autosomal dominant form of spinocerebellar ataxia (SCA1) has been assigned to the short arm of chromosome 6 on the basis of linkage to the major histocompatibility system (HLA). In this study of a five-generation American black family, close linkage between the disease locus and both HLA and the coagulation factor XIIIA (F13A1) locus was excluded, and lod scores for all locations of the disease locus between HLA and F13A1 were less than -1.4. These results suggest that the locus causing spinocerebellar ataxia in this family is not in this region. However, the disease locus was found to be closely linked to a microsatellite polymorphism, D6S89, which is between HLA and F13A1. The maximum lod score for SCA1 and D6S89 is 4.90 at a recombination fraction of 0, both in males and in females. These data show that exclusion of close linkage to the HLA complex and F13A1 in a kindred with spinocerebellar ataxia does not rule out the possibility that the disease locus in that family is on 6p. Accordingly, all families segregating a dominantly inherited ataxia should be evaluated for linkage to D6S89, to determine whether the locus causing the disease is SCA1.
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PMID:Tight linkage of the gene for spinocerebellar ataxia to D6S89 on the short arm of chromosome 6 in a kindred for which close linkage to both HLA and F13A1 is excluded. 192 3

We studied three large kindreds with the HLA-linked form of spinocerebellar ataxia (SCA1) in order to localize the SCA1 locus on the short arm of chromosome 6 (6p). Two loci containing highly informative dinucleotide repeat sequences were used for linkage analysis. These two loci are D6S89, which is telomeric to the HLA region, and T complex-associated testes-expressed 1 (TCTE1), centromeric to HLA. Pairwise linkage analysis of SCA1 and D6S89 revealed a maximum lod score of 5.86 in the Houston SCA1 (HSCA1) kindred and of 8.08 in the Calabrian SCA1 (SCA1) kindreds, at recombination fractions of .050 and .022, respectively. A maximum pairwise lod score of 4.54 at a recombination frequency of .100 was obtained for SCA1 and TCTE1 in the HSCA1 kindred. No evidence for linkage was detected between TCTE1 and SCA1 in the CSCA1 kindreds. Multilocus linkage analysis of SCA1, HLA, and D6S89 in all three kindreds provided strong evidence for localization of the SCA1 locus telomeric to the HLA regions. However, multilocus linkage analysis of SCA1, HLA, and TCTE1 with HSCA1 family genotypes indicated the possibility of a location of the SCA1 locus centromeric to HLA. An analysis of HSCA1 recombinants in this region of chromosome 6 revealed relatively high recombination frequencies between HLA and each of the other two markers and relatively low frequencies between the latter and SCA1, predicting that the SCA1 locus would tend to segregate away from HLA together with D6S89 or TCTE1, as found with the three-point linkage analyses for this family.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The gene for autosomal dominant spinocerebellar ataxia (SCA1) maps telomeric to the HLA complex and is closely linked to the D6S89 locus in three large kindreds. 206 71

Two families with autosomal dominant spinocerebellar ataxia (SCA) of late onset were studied. These families originate in the same small rural area in a Southern Italian region (Calabria). We report the clinical study of 23 patients in different stages of the disease and neuropathological study in one patient. Linkage studies provided strong evidence for linkage of the SCA locus to the HLA loci (SCA1) in the subjects of these families. Our study allows to outline the clinical features of HLA linked SCA in order to trace a pattern of SCA1 phenotype thus making easier the identification of SCA1 heterozygotes in an early clinical stage.
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PMID:[Clinical study of two families with late-onset autosomal dominant spinal-cerebellar ataxia linked with HLA. Preliminary results]. 210 35

A 7-generation kindred with the HLA-linked form of spinocerebellar ataxia (SCA1) was studied to determine whether the SCA1 gene maps centromeric or telomeric to the HLA loci. The DNA markers flanking the HLA-(A-B) region were used for polymorphism studies and multilocus linkage analysis. These two markers are the cDNA for the beta-subunit of HLA-DP, which is centromeric to HLA-(A-B), and the cDNA for coagulation factor XIIIa (F13A), which is telomeric to HLA-(A-B). Haplotypes were constructed using multiple polymorphisms for these two DNA markers, and pairwise linkage analysis revealed a maximum lod score of 2.18 for SCA1 versus HLA-DP at a recombination fraction of .05 and a maximum lod score of 0 for SCA1 versus F13A at a recombination fraction of .50. A possible crossover between HLA-(A-B) and HLA-DP was identified, but lack of samples from key individuals hampered the analysis. To clarify the phase and improve the analysis, the two chromosomes 6 for the crossover individual were separated in somatic cell hybrids. The results strongly favored the probability that the crossover occurred between HLA-(A-B-DR) and HLA-DP with SCA1 segregating with HLA-DP, consistent with a location centromeric to HLA-(A-B). Multilocus linkage analysis was used to evaluate further the location of SCA1 relative to F13A, HLA-(A-B), and HLA-DP; the results indicated that the SCA1 gene locus is centromeric to HLA-DP with odds of 46:1 favoring this most likely location over the second most likely location, i.e., telomeric to HLA-(A-B) between the HLA complex and F13A.
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PMID:Assignment of autosomal dominant spinocerebellar ataxia (SCA1) centromeric to the HLA region on the short arm of chromosome 6, using multilocus linkage analysis. 256 95


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