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1.
J. J. Magaña R. Gómez M. Maldonado-Rodríguez L. Velázquez-Pérez Y. S. Tapia-Guerrero H. Cortés N. Leyva-García O. Hernández-Hernández B. Cisneros 《Cerebellum (London, England)》2013,12(6):902-905
Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder characterized by progressive cerebellar ataxia associated with macular degeneration that leads, in the majority of patients, to loss of autonomy and blindness. The cause of the disease has been identified as (CAG) n repeat expansion in the coding sequence of the ATXN7 gene on chromosome 3p21.1. SCA7 is one of the least common genetically verified autosomal dominant cerebellar ataxias found worldwide; however, we previously identified the Mexican population showing high prevalence of SCA7, suggesting the occurrence of a common founder effect. In this study, haplotype analysis using four SCA7 gene-linked markers revealed that all 72 SCA7 carriers studied share a common haplotype, A-254-82-98, for the intragenic marker 3145G/A and centromeric markers D3S1287, D3S1228, and D3S3635, respectively. This multiloci combination is uncommon in healthy relatives and Mexican general population, suggesting that a single ancestral mutation is responsible for all SCA7 cases in this population. Furthermore, genotyping using 17 short tandem repeat markers from the non-recombining region of the Y chromosome and further phylogenetic relationship analysis revealed that Mexican patients possess the Western European ancestry, which might trace the SCA7 ancestral mutation to that world region. 相似文献
2.
Giovana?B.?Bampi Rafael?Bisso-Machado Tábita?Hünemeier Tailise?C.?Gheno Gabriel?V.?Furtado Diego?Veliz-Otani Mario?Cornejo-Olivas Pillar?Mazzeti Maria?Cátira?Bortolini Laura?B.?Jardim Maria?Luiza?Saraiva-Pereira 《Neuromolecular medicine》2017,19(4):501-509
Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia and epilepsy. The disease is caused by a pentanucleotide ATTCT expansion in intron 9 of the ATXN10 gene on chromosome 22q13.3. SCA10 has shown a geographical distribution throughout America with a likely degree of Amerindian ancestry from different countries so far. Currently available data suggest that SCA10 mutation might have spread out early during the peopling of the Americas. However, the ancestral origin of SCA10 mutation remains under speculation. Samples of SCA10 patients from two Latin American countries were analysed, being 16 families from Brazil (29 patients) and 21 families from Peru (27 patients) as well as 49 healthy individuals from Indigenous Quechua population and 51 healthy Brazilian individuals. Four polymorphic markers spanning a region of 5.2 cM harbouring the ATTCT expansion were used to define the haplotypes, which were genotyped by different approaches. Our data have shown that 19-CGGC-14 shared haplotype was found in 47% of Brazilian and in 63% of Peruvian families. Frequencies from both groups are not statistically different from Quechua controls (57%), but they are statistically different from Brazilian controls (12%) (p < 0.001). The most frequent expanded haplotype in Quechuas, 19-15-CGGC-14-10, is found in 50% of Brazilian and in 65% of Peruvian patients with SCA10. These findings bring valuable evidence that ATTCT expansion may have arisen in a Native American chromosome. 相似文献
3.
J. Vale P. Bugalho I. Silveira J. Sequeiros J. Guimarães P. Coutinho 《European journal of neurology》2010,17(1):124-128
Background and purpose: The relative frequency of the different autosomal dominant cerebellar ataxia (ADCA) varies widely amongst different geographic locations. Here we describe a series of 45 ADCA families from Portugal.
Methods: Patients with progressive cerebellar dysfunction of autosomal dominant transmission underwent a clinical examination protocol and genetic testing for spinocerebellar ataxia (SCA)1 to Machado-Joseph disease (MJD)/SCA3, SCA6, SCA7, SCA10, SCA12, SCA17 and dentatorubral-pallidoluysian atrophy (DRPLA). We registered the clinical characteristics and frequency of each type of ataxia.
Results: MJD/SCA3 was the most frequent ADCA (26 families, 57.8% of all families), followed by DRPLA (5 families, 11.2%), SCA7 (2 families, 4.4%), SCA2 and SCA1 (1 family each, 2.2% each); 10 families (22.2%) had no molecular diagnosis. SCA1 and SCA7 patients had African ancestry. DRPLA patients had Portuguese ancestry and were characterized by prominent anticipation and a variable combination of epilepsy, extra-pyramidal symptoms and dementia. Ophtalmoparesis, slow saccades and retinopathy were most distinctive of SCA3, SCA2 and SCA7 cases, respectively.
Conclusions: MJD/SCA3 was the most common ADCA in this group of families. The high frequency of DRPLA and presence of SCA1 and SCA7 cases was unexpected. The presence of these rarer ADCA types probably reflects migration phenomena, posing a challenge for differential diagnosis. 相似文献
Methods: Patients with progressive cerebellar dysfunction of autosomal dominant transmission underwent a clinical examination protocol and genetic testing for spinocerebellar ataxia (SCA)1 to Machado-Joseph disease (MJD)/SCA3, SCA6, SCA7, SCA10, SCA12, SCA17 and dentatorubral-pallidoluysian atrophy (DRPLA). We registered the clinical characteristics and frequency of each type of ataxia.
Results: MJD/SCA3 was the most frequent ADCA (26 families, 57.8% of all families), followed by DRPLA (5 families, 11.2%), SCA7 (2 families, 4.4%), SCA2 and SCA1 (1 family each, 2.2% each); 10 families (22.2%) had no molecular diagnosis. SCA1 and SCA7 patients had African ancestry. DRPLA patients had Portuguese ancestry and were characterized by prominent anticipation and a variable combination of epilepsy, extra-pyramidal symptoms and dementia. Ophtalmoparesis, slow saccades and retinopathy were most distinctive of SCA3, SCA2 and SCA7 cases, respectively.
Conclusions: MJD/SCA3 was the most common ADCA in this group of families. The high frequency of DRPLA and presence of SCA1 and SCA7 cases was unexpected. The presence of these rarer ADCA types probably reflects migration phenomena, posing a challenge for differential diagnosis. 相似文献
4.
Koht J Stevanin G Durr A Mundwiller E Brice A Tallaksen CM 《Acta neurologica Scandinavica》2012,125(2):116-122
Koht J, Stevanin G, Durr A, Mundwiller E, Brice A, Tallaksen CME. SCA14 in Norway, two families with autosomal dominant cerebellar ataxia and a novel mutation in the PRKCG gene. Acta Neurol Scand: 2012: 125: 116–122. © 2011 John Wiley & Sons A/S. Objectives – Despite a similar prevalence of autosomal dominant cerebellar ataxia (ADCA) in Norway compared to other European countries, less than 10% of the families are explained by the CAG trinucleotide expansions. We wanted to find the occurence of SCA14 in the dominant ataxia population and describe the phenotype. Methods – We screened a large dominant cerebellar ataxia cohort for mutations in the PRKCG gene. Patients were evaluated according to a standard clinical protocol for ataxia patients. Results – A novel mutation was found in two families, a C to A transversion altering Histidine to a Glutamine at codon 139, located in a highly concerved region in the gene. It completely co‐segregated with the affected family members and was not seen in 576 control chromosomes. Genetic analysis revealed common alleles at three microsatellite markers between these two families suggesting a shared ancestral chromosome. Affected subjects displayed a mild, slowly progressive cerebellar syndrome that included gait and limb ataxia and saccadic pursuit and head tremor in one. Age at onset ranged from 10 to 45 years. Conclusions – These are the first families with SCA14 reported from Scandinavia and a new mutation in the PRKCG gene. The occurrence in the Norwegian dominant ataxia cohort is 3.5%. 相似文献
5.
OBJECTIVE: To investigate the clinical and molecular characteristics of spinocerebellar ataxia type 7 (SCA7) in Chinese kindreds. BACKGROUND: Spinocerebellar ataxia type 7 is caused by the expansion of an unstable CAG repeat in the first exon of the SCA7 gene. METHODS: Clinical and related examinations were performed in all affected or at-risk individuals from 4 Chinese families presenting with autosomal dominant cerebellar ataxia and decreased visual acuity. The size of the (CAG)(n) array of the SCA7 gene was detected by polymerase chain reaction, polyacrylamide gel electrophoresis, and related techniques in the 4 families and 67 healthy controls. The relationship between expanded repeat number and age of onset was statistically analyzed. RESULTS: The SCA7 mutation was identified in 2 families. Clinical study revealed that great variation occurred in the age of onset, initial symptoms, and associated signs. Meanwhile, the analysis of 11 parent-child couples demonstrated the existence of marked anticipation. Some distinct retinal changes were noted in 2 affected patients. All SCA7 patients in our series exhibited expanded CAG repeats, ranging from 44 to 85 repeats, with a strong negative correlation between repeat size and age of onset. Repeat lengths of expanded alleles showed somatic mosaicism in leukocyte DNA. There were some subtle clinical differences between the SCA7-positive and -negative cases. CONCLUSIONS: Clinical variation occurred not only among the SCA7 families but also within the same kindred. Meiotic and mitotic instability of the CAG repeat in the SCA7 gene were demonstrated, and intergenerational instability of the array was associated with the clinical phenomenon of anticipation. Arch Neurol. 2000;57:1513-1518 相似文献
6.
Analysis of trinucleotide repeats in different SCA loci in spinocerebellar ataxia patients and in normal population of Taiwan 总被引:8,自引:0,他引:8
Tsai HF Liu CS Leu TM Wen FC Lin SJ Liu CC Yang DK Li C Hsieh M 《Acta neurologica Scandinavica》2004,109(5):355-360
Objective – To identify various subtypes of spinocerebellar ataxias (SCAs) among autosomal dominant cerebellar ataxia (ADCA) patients referred to our research center, SCA1, SCA2, SCA3/MJD (Machado–Joseph disease), SCA6, SCA7, SCA8 and SCA12 loci were assessed for expansion of trinucleotide repeats.
Patients and methods – A total of 211 ADCA patients, including 202 patients with dominantly inherited ataxia from 81 Taiwanese families and nine patients with sporadic ataxia, were included in this study and subjected to polymerase chain reaction (PCR) analysis. The amplified products of all loci were analyzed on both 3% agarose gels and 6% denaturing urea-polyacrylamide gels. PCR-based Southern blots were also applied for the detection of SCA7 locus.
Results – The SCA1 mutation was detected in six affected individuals from one family (1.2%) with expanded alleles of 50–53 CAG repeats. Fourteen individuals from nine families (11%) had a CAG trinucleotide repeat expansion at the SCA2 locus, while affected SCA2 alleles have 34–49 CAG repeats. The SCA3/MJD CAG trinucleotide repeat expansion in 60 affected individuals from 26 families (32%) was expanded to 71–85 CAG repeats. As for the SCA7 locus, there were two affected individuals from one family (1.2%) possessed 41 and 100 CAG repeats, respectively. However, we did not detect expansion in the SCA6, SCA8 and SCA12 loci in any patient.
Conclusions – The SCA3/MJD CAG expansion was the most frequent mutation among the SCA patients. The relative prevalence of SCA3/MJD in Taiwan was higher than that of SCA2, SCA1 and SCA7. 相似文献
Patients and methods – A total of 211 ADCA patients, including 202 patients with dominantly inherited ataxia from 81 Taiwanese families and nine patients with sporadic ataxia, were included in this study and subjected to polymerase chain reaction (PCR) analysis. The amplified products of all loci were analyzed on both 3% agarose gels and 6% denaturing urea-polyacrylamide gels. PCR-based Southern blots were also applied for the detection of SCA7 locus.
Results – The SCA1 mutation was detected in six affected individuals from one family (1.2%) with expanded alleles of 50–53 CAG repeats. Fourteen individuals from nine families (11%) had a CAG trinucleotide repeat expansion at the SCA2 locus, while affected SCA2 alleles have 34–49 CAG repeats. The SCA3/MJD CAG trinucleotide repeat expansion in 60 affected individuals from 26 families (32%) was expanded to 71–85 CAG repeats. As for the SCA7 locus, there were two affected individuals from one family (1.2%) possessed 41 and 100 CAG repeats, respectively. However, we did not detect expansion in the SCA6, SCA8 and SCA12 loci in any patient.
Conclusions – The SCA3/MJD CAG expansion was the most frequent mutation among the SCA patients. The relative prevalence of SCA3/MJD in Taiwan was higher than that of SCA2, SCA1 and SCA7. 相似文献
7.
Ethnic differences in the expression of neurodegenerative disease: Machado-Joseph disease in Africans and Caucasians. 总被引:2,自引:0,他引:2
S H Subramony Dena Hernandez Amanda Adam Stephanie Smith-Jefferson Jennifer Hussey Katrina Gwinn-Hardy Timothy Lynch Olga McDaniel John Hardy Matt Farrer Andrew Singleton 《Movement disorders》2002,17(5):1068-1071
We describe several families of African origin with SCA3/Machado-Joseph disease gene expansions. In these cases, the phenotype ranges from ataxia with parkinsonian signs to a syndrome clinically almost indistinguishable from idiopathic, L-dopa-responsive Parkinson's disease. In contrast, these parkinsonian phenotypes are rare in those of European descent. Haplotype analysis shows that these African families do not share a common founder, thus a cis-acting element in the promoter is unlikely to be responsible these unusual presentations. We suggest that trans-acting factors are responsible for the variable phenotype and discuss the implications of diseases showing racially different expressivities. 相似文献
8.
M. Traor T. Coulibaly K. G. Meilleur A. La Pean M. Sangar G. Landour F. Mochel M. Karamb C. O. Guinto K. H. Fischbeck 《European journal of neurology》2011,18(10):1269-1271
Background: Autosomal dominant cerebellar ataxia, currently denominated spinocerebellar ataxia (SCAs), represents a heterogeneous group of neurodegenerative disorders affecting the cerebellum and its connections. We describe the clinical and molecular findings in 16 patients originating from Malian families, who suffer from progressive cerebellar ataxia syndrome. Methods and results: Molecular analysis allows genetic profiles of SCA to be distinguished. In seven patients, SCA type 2 (CAG) mutation was expanded from 39 to 43 repeats. SCA type 7 (CAG) mutation was confirmed in six patients. Mutations were expanded from 49 to 59 repeats. In three patients, SCA type3 was diagnosed and CAG mutation was expanded to 73 repeats. Conclusions: Our data suggest that the most frequent types of SCA are SCA2 and SCA7. However, further studies are needed to confirm these preliminary results. 相似文献
9.
Spinocerebellar ataxia (SCA) type 7 is an autosomal dominant disorder characterized by neural loss, mainly in the cerebellum and regions of the brainstem and particularly the inferior olivary complex. This neurodegeneration disease is associated with expansion of unstable CAG repeats within the 5'-translated region of the SCA7 gene, located on chromosome 3p. We conducted a local survey of the normal population and candidate patients for the analysis of the CAG repeats in the SCA7 gene. The distributions of the CAG repeat units of SCA7 gene in the normal population in Taiwan were established in this study by using the radioactive genomic polymerase chain reaction (PCR). The normal range of CAG repeats is from 6 to 17 repeats, with the more common being around 8-13 repeats. The range is narrower than that reported for other ethnic groups (7-35 CAGs). Meanwhile, by the use of a combination of PCR and Southern blot analysis, one SCA7 family was identified and is reported here. A marked instability of the CAG repeat number during transmission from father to son (41 vs. 100) was observed in the SCA7 family. Clinical anticipation is significant in this family including an infantile case, who was found to have nystagmus from the age of 1 month. To date, the SCA7 mutation has been detected in one of 73 families with autosomal dominant cerebellar ataxia phenotypes, which is about 1.4% of the ataxia families referred to us, compared to 1.4% SCA1, 9.6% SCA2, and 27.3% SCA3/Machado-Joseph disease in our collection. In addition, we demonstrate that the PCR-based Southern blot analysis, with the advantages of sensitivity of PCR and specificity of Southern blot, is a reliable diagnostic method for SCA7 mutation screening. The molecular analysis technique makes possible the quick and accurate diagnosis of SCA7 patients and in the future will hopefully be applied to prenatal screening for SCA7 families. 相似文献
10.
Anna Sułek-Piątkowska Elżbieta Zdzienicka Maria Rakowicz Wioletta Krysa Marta Rajkiewicz Walentyna Szirkowiec Jacek Zaremba 《Neurologia i neurochirurgia polska》2010,44(3):238-245
Background and purposeAutosomal dominant spinocerebellar ataxias (SCAs) belong to a group of neurodegenerative disorders usually of adult age at onset. Predominant clinical features are progressive ataxia, dysarthria, as well as pyramidal signs and polyneuropathy. Molecular analysis allows particular types of SCA to be distinguished. Genetic tests are applied in 10 types of SCA resulting from dynamic mutations: SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA10, SCA12, SCA17 and DRPLA.Material and methodsDNA samples from 1598 patients with ataxia symptoms were analysed to establish the number of CAG/CTG repeats in respective genes excluding SCA10.ResultsWe diagnosed 224 cases of SCA1 (120 families) and 49 cases of SCA2 (23 families). Moreover, presymptomatic testing was done in 85 individuals from SCA1 families and for 21 cases from SCA2 families. An increased number of CTG repeats in the SCA8 gene was observed in 14 families and in 3 families a rare type of SCA, SCA17, was detected.ConclusionsOur data suggest that frequencies of some types of SCA in Poland are different from those in other European countries, with irregular distribution within the country. The most frequent types are SCA1 and SCA2. A striking feature of the Polish population is the lack of SCA3 – the most frequent type in Western Europe. 相似文献
11.
Spinocerebellar ataxia type 3 phenotypically resembling parkinson disease in a black family 总被引:4,自引:0,他引:4
Gwinn-Hardy K Singleton A O'Suilleabhain P Boss M Nicholl D Adam A Hussey J Critchley P Hardy J Farrer M 《Archives of neurology》2001,58(2):296-299
BACKGROUND: Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), can present with parkinsonism. However, classically, atypical features, including pyramidal and cerebellar signs, peripheral neuropathy, and/or anterior horn cell dysfunction, are also seen. Levodopa responsiveness is unusual in this disorder. OBJECTIVE: To determine the cause of apparent parkinsonism suggestive of Parkinson disease (PD) in a large family of African origin. METHODS: We studied a large family in which apparent autosomal dominant parkinsonism suggestive of PD occurs in order to find the causal genetic mutation. Affected and unaffected family members were screened for the presence of a pathogenic expansion at the MJD/SCA3 locus using a polymerase chain reaction polyacrylamide gel electrophoresis-based assay. RESULTS: Three of the 4 individuals who were examined have a phenotype reminiscent of PD. Specifically, they have at least 2 of the cardinal features, are levodopa responsive, and have no atypical features. All affected family members were shown to possess pathogenic expansions in the MJD/SCA3 gene. CONCLUSIONS: Parkinsonism suggestive of PD due to MJD/SCA3 has not been previously reported, to our knowledge. However, atypical, though also levodopa-responsive, parkinsonism has been previously reported to occur in African American families, suggesting that that this phenotype is associated with African ancestry. In this regard, it is perhaps significant that all the individuals with parkinsonism have relatively low numbers of repeats (normal, 16-34; pathologic, 60-84). In families in which linkage analysis is being performed to determine a locus for autosomal dominant parkinsonism suggestive of PD, evaluation for the MJD/SCA3 mutation is indicated. 相似文献
12.
Spinocerebellar ataxia type 6: evidence for a strong founder effect among German families 总被引:2,自引:0,他引:2
Dichgans M Schöls L Herzog J Stevanin G Weirich-Schwaiger H Rouleau G Bürk K Klockgether T Zühlke C Laccone F Riess O Gasser T 《Neurology》1999,52(4):849-851
The authors found a strong geographic cluster of spinocerebellar ataxia type 6 (SCA6) families in the Northrhine-Westfalia area, suggesting a founder effect in the German SCA6 population. Genotyping with DNA markers linked to the CACNL1A4 gene on chromosome 19p13 revealed a common haplotype and shared allelic characteristics in the majority of German families. The observed founder effect may be related to the relative meiotic stability of CAG repeats in this type of autosomal dominant cerebellar ataxia. 相似文献
13.
Relative frequencies of CAG expansions in spinocerebellar ataxia and dentatorubropallidoluysian atrophy in 116 Italian families 总被引:1,自引:0,他引:1
Filla A Mariotti C Caruso G Coppola G Cocozza S Castaldo I Calabrese O Salvatore E De Michele G Riggio MC Pareyson D Gellera C Di Donato S 《European neurology》2000,44(1):31-36
Two hundred and forty-eight patients from 116 Italian families with dominant ataxia were studied for CAG expansion within SCA1, 2, 3, 6, 7 (spinocerebellar ataxia) and DRPLA (dentatorubropallidoluysian atrophy) genes. Fifty-six percent of the families originated from Southern, 19% from Central and 25% from Northern Italy. SCA2 was the commonest mutation, accounting for 47% of the families, followed by SCA1 (24%), SCA6 (2%), SCA7 (2%) and DRPLA (1%). No SCA3 family was found. Twenty-four percent of the families carried a still unidentified mutation. When occurrence of mutations was evaluated according to the geographic origin, SCA1 was the commonest in Northern (72%), whereas SCA2 was prevalent (63%) in Southern Italy. The number of CAG repeats in SCA1 normal alleles was higher in Northern than in Central-Southern Italy. 相似文献
14.
Masanori Kurihara Hiroyuki Ishiura Takuya Sasaki Juuri Otsuka Toshihiro Hayashi Yasuo Terao Takashi Matsukawa Jun Mitsui Juntaro Kaneko Kazutoshi Nishiyama Koichiro Doi Jun Yoshimura Shinichi Morishita Jun Shimizu Shoji Tsuji 《Cerebellum (London, England)》2018,17(2):237-242
Spinocerebellar ataxia 19/22 (SCA19/22) is a rare type of autosomal dominant SCA that was previously described in 11 families. We report the case of a 30-year-old Japanese man presenting with intellectual disability, early onset cerebellar ataxia, myoclonus, and dystonia without a family history. MRI showed cerebellar atrophy, and electroencephalograms showed paroxysmal sharp waves during hyperventilation and photic stimulation. Trio whole-exome sequencing analysis of DNA samples from the patient and his parents revealed a de novo novel missense mutation (c.1150G>A, p.G384S) in KCND3, the causative gene of SCA19/22, substituting for evolutionally conserved glycine. The mutation was predicted to be functionally deleterious by bioinformatic analysis. Although pure cerebellar ataxia is the most common clinical feature in SCA19/22 families, extracerebellar symptoms including intellectual disability and myoclonus are reported in a limited number of families, suggesting a genotype–phenotype correlation for particular mutations. Although autosomal recessive diseases are more common in patients with early onset sporadic cerebellar ataxia, the present study emphasizes that such a possibility of de novo mutation should be considered. 相似文献
15.
OBJECTIVE: To assess the frequency of SCA1 (spinocerebellar ataxia type 1), SCA2, SCA3/MJD (spinocerebellar ataxia type 3/Machado-Joseph disease), SCA6, SCA7, and DRPLA (dentatorubropallidoluysian atrophy) CAG trinucleotide repeat expansions [(CAG)n] among persons diagnosed with hereditary SCA from Chinese families. PATIENTS AND METHODS: Spinocerebellar ataxia type 1, SCA2, SCA3/MJD, SCA6, SCA7, and DRPLA (CAG)n mutation were detected with the polymerase chain reaction, highly denaturing polyacrylamide gel electrophoresis, and silver staining technique in 167 patients with autosomal dominant SCA from 85 Chinese families and 37 patients with sporadic SCA. RESULTS: Spinocerebellar ataxia type 1 (CAG)n mutation in 7 patients from 4 kindreds (4.70%) was expanded to 53 to 62 repeats. Spinocerebellar ataxia type 2 (CAG)n mutation in 12 patients from 5 kindreds (5.88%) was expanded to 42 to 47 repeats. Spinocerebellar ataxia type 3/Machado-Joseph disease (CAG)n mutation in 83 patients from 41 kindreds (48.23%) was expanded to 68 to 83 repeats. Sixty-five patients from 35 kindreds (41.19%) and 37 patients with sporadic SCA did not test positive for SCA1, SCA2, SCA3/MJD, SCA6, SCA7, or DRPLA. There was a predictable inverse relationship between the number of CAG repeats and the age at onset for SCA3/MJD and SCA2. Clinically, dementia and hyporeflexia were more frequent in patients with SCA2, while spasticity, hyperreflexia, and Babinski signs were more frequent in patients with SCA3/ MJD, and those might be helpful in clinical work to primarily distinguish patients with SCA3/MJD and SCA2 from others with different types of SCA. CONCLUSIONS: The frequency of SCA3/MJD is substantially higher than that of SCA1 and SCA2 in patients with autosomal dominant SCA from Chinese kindreds, who are non-Portuguese. Clinical expressions of the various types of SCAs overlap one another; therefore, for clinical study it is important to make a gene diagnosis and genetic classification for patients with SCA. 相似文献
16.
Teive HA Roa BB Raskin S Fang P Arruda WO Neto YC Gao R Werneck LC Ashizawa T 《Neurology》2004,63(8):1509-1512
Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant ataxia caused by an ATTCT repeat expansion in an intron of the SCA10 gene. SCA10 has been reported only in Mexican families, in which the disease showed a combination of cerebellar ataxia and epilepsy. The authors report 28 SCA10 patients from five new Brazilian families. All 28 patients showed cerebellar ataxia without epilepsy, suggesting that the phenotypic expression of the SCA10 mutation differs between Brazilian and Mexican families. 相似文献
17.
目的 探讨遗传性脊髓小脑型共济失调(SCA)7型(SCA7)的临床特征和基因突变.方法 采用聚合酶链反应(PCR)和琼脂糖凝胶电泳(AGE)等技术,检测临床诊断为SCA的5个家系26例患者和37例表型正常的家系成员的SCA7基因内CAG三核苷酸重复次数,对异常等位基因片段进行DNA测序,分析临床表现和基因突变的关系. 结果 2个SCA7家系患者的SCA7等位基因内CAG重复数目为44~50次;临床表现主要为共济失调、视力下降及视网膜色素变性.该家系内表型正常的家系成员SCA7等位基因CAG重复数目为10~30. 结论 CAG过度扩增为SCA7的致病原因,分子遗传学分析有助于SCA7的诊断. 相似文献
18.
M. Hsieh S.-Y. Li C.-J. Tsai Y.-Y. Chen C.-S. Liu C.-Y. Chan L.-S. Ro D.-F. Chen S.-S. Chen C. Li 《Acta neurologica Scandinavica》1999,100(3):189-194
OBJECTIVES: The autosomal dominant cerebellar ataxias (ADCAs) are a group of genetically diverse neurological conditions linked by progressive deterioration in balance and coordination. Spinocerebellar Ataxia Type 2 (SCA2) is one of the ADCAs and also belongs to a special group caused by the expansion of an unstable CAG repeat encoding a polyglutamine tract. We aimed to investigate the frequency of SCA2 mutation in the ataxia patients referred to the clinic. MATERIALS AND METHODS: We screened 58 families with inherent cerebellar ataxia and 57 normal individuals by the use of radioactive genomic polymerase chain reaction (PCR) method. A simple non-radioactive PCR for rapid detection of the expanded SCA2 alleles via agarose gel electrophoresis was also employed. RESULTS: Eight SCA2 affected patients and 1 at-risk individual in 5 unrelated SCA2 families were identified. The CAG repeats of normal alleles in the sample studied range in size from 16 to 30 repeat units, while those of SCA2 chromosomes are expanded to 34 to 49 repeat units. Our results also showed that unlike SCA 1 and SCA3/MJD, the size distribution of the normal alleles showed few polymorphisms, with the 22 repeat allele accounting for 90.1%. Homozygosity in normal individuals was 80.2%. No overlap in ataxin-2 allele size between normal and expanded chromosomes was observed. CONCLUSION: This is the first report of the SCA2 gene distributions in the population of Taiwan. The SCA2 mutation accounts for 8.6% of ADCA type I families referred to us, intermediate between SCA1(1.7%) and SCA3/MJD (24%) of the ADCA type I families in our collection. 相似文献
19.
Natasa T Dragasevi? Biljana Culjkovi? Christine Klein Aleksandar Risti? Milica Keckarevi? Ivan Topisirovi? Slobodanka Vukosavi? Marina Svetel Norman Kock Elka Stefanova Stanka Romac Vladimir S Kosti? 《Movement disorders》2006,21(2):187-191
The relative frequencies of different spinocerebellar ataxias (SCAs) vary widely among different ethnic groups, presumably due to a founder effect. We investigated the relative prevalence of SCA1-3, 6-8, 12, 17; dentate-rubro-pallidoluysian atrophy; and Friedreich's ataxia (FRDA) in Serbian patients with adult-onset (>20 years of age) hereditary and sporadic SCAs, and compared clinical features of patients with genetically confirmed SCAs. A total of 108 patients from 54 families (38 apparently dominant [ADCA] and 16 apparently recessive) with adult-onset hereditary ataxia and 75 apparently sporadic patients were assessed. Of 38 families with ADCA, 13 (34%) were positive for an expansion in an SCA1 and 5 families (13%) for an expansion in an SCA2 allele. In 20 families (53%), no expansions have been identified in any of the analyzed genes. Gaze palsy, spasticity, and hyperreflexia were significantly more common in SCA1, whereas slow saccades, hypotonia, hyporeflexia, and dystonia prevailed in SCA2 patients. Among the 16 families with an apparently recessive mode of ataxia inheritance, 4 (25%) were identified as having the FRDA mutation. Ataxia-causing mutations were identified in 8 (10.6%) of patients with apparently sporadic adult-onset ataxia. 相似文献
20.
O. Dubourg A. Dürr G. Cancel G. Stevanin C. Penet Y. Agid A. Brice H. Chneiweiss 《Annals of neurology》1995,37(2):176-180
Autosomal dominantly inherited ataxias are a clinically and genetically heterogeneous group of neurodegenerative disorders. The gene involved in one subtype, spinocerebellar ataxia 1 (SCA I), was first localized to chromosome 6p. An unstable CAG repeat has been identified as the responsible mutation. In this study, 88 families with various types of inherited ataxias and 16 individuals with sporadic cerebellar ataxia were investigated to determine the frequency of this mutation, the behavior of the SCA1 CAG repeat during transmission, and the clinical features specific to this form of disease. Only 12 of the families carried the SCA1 mutation; 10 of the 12 were of French origin. When transmitted paternally, the repeat was more unstable and larger in size. Age at onset was inversely correlated with the number of CAG repeats. Anticipation in age at onset of about 11 years was observed in offspring. Analysis of the clinical features did not distinguish SCA1 from other forms of dominantly inherited ataxias. In the absence of distinguishing clinical characteristics, the diagnosis of SCA1 in single affected patients or family members can only be made by direct detection of the mutation, opening the way for presymptomatic testing. 相似文献