Analysis of SCA1, DRPLA, MJD, SCA2, and SCA6 CAG repeats in 48 portuguese ataxia families

Silveira, Isabel; Coutinho, Paula; Maciel, Patrı́cia; Gaspar, Cláudia; Hayes, Sean M.; Dias, Ana Cláudia; Guimarães, João Tiago; Loureiro, José Leal; Sequeiros, Jorge; Rouleau, Guy A.

doi:10.1002/(sici)1096-8628(19980328)81:2<134::aid-ajmg3>3.0.co;2-w

Cited by 59 publications

(28 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compared with the averaged frequency of ADCA subtypes in other districts of Japan (Table 1) (Takano et al 1998;Sasaki et al 2003), the low frequency of SCA3/MJD is characteristic of Nagano. SCA3/MJD is the most prevalent ADCA subtype in Japan (Table 1) as well as in the majority of countries (Jardim et al 2001;Tang et al 2000;Stevanin et al 1997;van de Warrenburg et al 2002;Silveira et al 1998;Soong et al 2001). This is also the case in the Niigata (43%) and Nagoya (39%) districts, which are geographically adjacent to Nagano; therefore, the low frequency of SCA3/MJD in Nagano (3%) is noteworthy.…”

Section: Discussionmentioning

confidence: 93%

“…Several studies have indicated that SCA6, SCA3/MJD, and DRPLA are the most prevalent subtypes of ADCA in Japan despite a considerable variation in the frequency of each subtype among districts . The frequency of ADCA subtypes also varies among countries (Jardim et al 2001;Tang et al 2000;Stevanin et al 1997;van de Warrenburg et al 2002;Silveira et al 1998;Soong et al 2001).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Regional features of autosomal-dominant cerebellar ataxia in Nagano: clinical and molecular genetic analysis of 86 families

Shimizu¹,

Yoshida

Okano³

et al. 2004

J Hum Genet

View full text Add to dashboard Cite

The frequency of autosomal-dominant cerebellar ataxia (ADCA) subtypes was examined in 86 unrelated families originating from Nagano prefecture. In Nagano, the prevalence of spinocerebellar degeneration (SCD) was approximately 22 per 100,000 population. Among ADCA families, SCA6 was the most prevalent subtype (16 families, 19%), followed by DRPLA (nine families, 10%), SCA3/MJD (three families, 3%), SCA1 (two families, 2%), and SCA2 (one family, 1%). No families with SCA7, SCA12, or SCA17 were detected. Compared with other districts in Japan, the prevalence of SCA3/MJD was very low in Nagano. More interestingly, the ratio of genetically undetermined ADCA families was much higher in Nagano (55 families, 65%) than in other districts in Japan. These families tended to accumulate in geographically restricted areas such as Kiso, Saku, and Ina, indicating that the founder effect might be responsible for the high frequency of ADCA in these areas. Most patients clinically showed slowly progressive pure cerebellar ataxia of late-onset (ADCA III). In the case of 36 patients from 36 genetically undetermined ADCA III families, however, no one was completely consistent with the founder allele proposed for 16q-ADCA. These results indicate that there might be genetically distinct ADCA subtypes in Nagano.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Regional features of autosomal-dominant cerebellar ataxia in Nagano: clinical and molecular genetic analysis of 86 families

Shimizu¹,

Yoshida

Okano³

et al. 2004

J Hum Genet

View full text Add to dashboard Cite

show abstract

“…To date, at least 29 of them have been mapped, and 15 genes have been identified. An exonic unstable CAG repeat expansion is the most frequent mutation associated with this group of neurodegenerative disorders 1 . Machado Joseph disease (MJD) or spinocerebellar ataxia type 3 (MJD/SCA3) seems to be the most common late-onset spinocerebellar ataxia in many world regions, including Germany, Brazil, Portugal, India, France, North America, Japan, China and Taiwan [1][2][3][4][5] .…”

Section: Machado Joseph Disease: Volumetric Analysismentioning

confidence: 99%

Brain stem and cerebellum volumetric analysis of Machado Joseph disease patients

Camargos

Marques-Jr

Santos

2011

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

Machado-Joseph disease, or spinocerebellar ataxia type 3(MJD/SCA3), is the most frequent late onset spinocerebellar ataxia and results from a CAG repeat expansion in the ataxin-3 gene. Previous studies have found correlation between atrophy of cerebellum and brainstem with age and CAG repeats, although no such correlation has been found with disease duration and clinical manifestations. In this study we test the hypothesis that atrophy of cerebellum and brainstem in MJD/SCA3 is related to clinical severity, disease duration and CAG repeat length as well as to other variables such as age and ICARS (International Cooperative Ataxia Rating Scale). Whole brain high resolution MRI and volumetric measurement with cranial volume normalization were obtained from 15 MJD/ SCA3 patients and 15 normal, age and sex-matched controls. We applied ICARS and compared the score with volumes and CAG number, disease duration and age. We found significant correlation of both brain stem and cerebellar atrophy with CAG repeat length, age, disease duration and degree of disability. The Spearman rank correlation was stronger with volumetric reduction of the cerebellum than with brain stem. Our data allow us to conclude that volumetric analysis might reveal progressive degeneration after disease onset, which in turn is linked to both age and number of CAG repeat expansions in SCA 3. Key words: CAG expansion, Machado-Joseph disease, MJD/SCA3, spinocerebellar ataxia, volumetry.Análise volumétrica de cerebelo e tronco cerebral de pacientes com doença de Machado Joseph RESUMO Doença de Machado-Joseph, ou ataxia espinocerebelar tipo 3 (MJD/SCA3) é ataxia espinocerebelar de início tardio mais frequente e resulta de uma expansão da repetição CAG no gene da ataxina-3. Estudos precedentes encontraram correlação entre a atrofia do cerebelo e do tronco cerebral com a idade e número de expansões CAG. Tais correlações não foram encontradas em relação ao tempo de doença ou manifestações clínicas. Neste estudo testamos a hipótese de que a atrofia do cerebelo e do tronco encefálico em MJD/SCA3 está relacionada à gravidade clínica, duração da doença e número de repetições CAG, bem como com outras variáveis como a idade e a ICARS (escala cooperativa internacional de avaliação de ataxias). Foram realizados estudos de imagem pela ressonância magnética de alta resolução e volumetria com normalização de volume craniano de 15 pacientes portadores de MJD/SCA3 e 15 controles pareados por idade e sexo. Nós aplicamos a ICARS e correlacionamos com o escore de volumes e número de CAG, duração da doença e idade. Encontramos correlação significativa entre atrofia de tronco cerebral e cerebelo com duração da doença, repetição CAG, idade e grau de acometimento da doença. O índice de correlação de Spearman foi maior em relação à atrofia de cerebelo do que à atrofia de tronco. Nossos dados permitem concluir que a análise volumétrica pode revelar degeneração progressiva após o início da doença que, por sua vez, está ligada à idade e número de expansões CAG em SCA 3...

show abstract

“…40 The relative frequencies of the different CAG repeat expansions have been determined by molecular typing in several populations. [41][42][43][44][45][46][47][48][49][50][51][52][53][54] However, most of the large series do not clearly indicate the ethnic and/or geographical origin of the families. Although in most countries SCA3/MJD is the major locus, the relative frequencies of SCAs vary widely according to the geographical origin.…”

Section: Frequency and Origin Of The Mutationsmentioning

confidence: 99%

Clinical and molecular advances in autosomal dominant cerebellar ataxias: from genotype to phenotype and physiopathology

2000

View full text Add to dashboard Cite

Major advances have been made in the understanding of autosomal dominant cerebellar ataxias since genetic markers came into use in the 1980s. The subsequent mapping of nine genes, six of which have been identified, involved in this clinically diverse group of disorders highlighted their great genetic heterogeneity. Evidence is now accumulating that, except for SCA8, the same molecular and physiopathological processes underlie these diseases and other neurodegenerative disorders sharing the same mutational basis, the expansion of a (CAG)n-polyglutamine coding sequence. The clinical overlap among the different genetic entities makes prediction of the molecular origin impossible in a single patient so that molecular characterisation is necessary. However, extended clinical and neuropathological comparisons have shown that each genetic entity has a characteristic constellation of signs and symptoms that are related to CAG repeat size and disease duration. The combined genetic and clinical information form the basis of a new classification that will aid better understanding of disease evolution, assure follow up and permit genetic counselling by the clinician.

show abstract

Analysis of SCA1, DRPLA, MJD, SCA2, and SCA6 CAG repeats in 48 portuguese ataxia families

Cited by 59 publications

References 30 publications

Regional features of autosomal-dominant cerebellar ataxia in Nagano: clinical and molecular genetic analysis of 86 families

Regional features of autosomal-dominant cerebellar ataxia in Nagano: clinical and molecular genetic analysis of 86 families

Brain stem and cerebellum volumetric analysis of Machado Joseph disease patients

Clinical and molecular advances in autosomal dominant cerebellar ataxias: from genotype to phenotype and physiopathology

Contact Info

Product

Resources

About