Autosomal Dominant Pure Cerebellar Ataxia

Frontali, Marina; Spadaro, M; Giunti, Paola; Bianco, Federico; Jodice, Carla; Persichetti, Francesca; Colazza, G. B.; Lulli, Patrizia; Terrenato, L.; Morocutti, C

doi:10.1093/brain/115.6.1647

Cited by 12 publications

(8 citation statements)

References 3 publications

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“…ADCA type II is characterized by the association of cerebellar ataxia with progressive macular degeneration (Froment et al, 1937;Benomar et al, 1994). ADCA type III denotes a ÔpureÕ cerebellar syndrome (Frontali et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Absence of spinocerebellar ataxia type 3/Machado–Joseph disease within ataxic patients in the Czech population

Bauer

Zumrová

Maťoška

et al. 2005

Euro J of Neurology

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Although spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease is the most common type of SCA worldwide, we did not identify any cases of the disease amongst SCA patients in the Czech population. It has been proposed that the prevalence of large normal alleles correlates with the frequency of various types of SCA. We have therefore attempted to resolve the absence of SCA3 in our population by investigating, within 204 normal chromosomes, the frequency and nature of CAG repeats as well as two intragenic polymorphisms. We found that large normal alleles with more than 33 CAG repeats were observed at a frequency of only 0.49%. Whereas most of the expanded alleles worldwide have the CA haplotype, this was the least common (5.4%) variant observed in our study, although it was associated with a larger mean CAG repeat length (26.9). We postulate that the absence of SCA3 in the Czech population might be explained by the lack of large normal alleles and consequently a relatively small reservoir for aberrant CAG expansions at the SCA3 locus.

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Section: Introductionmentioning

confidence: 99%

Absence of spinocerebellar ataxia type 3/Machado–Joseph disease within ataxic patients in the Czech population

Bauer

Zumrová

Maťoška

et al. 2005

Euro J of Neurology

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“…Second, an unexpected rapid disease progression was observed in Cases 3 and 4. They became unable to walk within 5 years after onset, in'striking contrast to the prior descriptions of SCA6 or ADCA type 3 in which it took over 20-30 years to become wheelchair-bound (1,10,12,17). Furthermore, the degree of ataxia was not uniformly mild; Case 1 showed severe truncal ataxia with neck shaking involuntary movement, although limb ataxia was mild; Cases 3 and 4 exhibited both severe truncal and limb ataxia.…”

Section: Discussionmentioning

confidence: 62%

“…In our study, the normal alleles of the SCA6 gene were between 4 and 13 CAG repeat units, while the expanded alleles ranged from 23 to 25 repeat units ( Table 1). From a clinical viewpoint, affected individuals of ADCA type 3 have been considered to exhibit a rather uniform clinical phenotype with late onset of the disease (around 50 years old), mild cerebellar ataxia, slows disease progression and there is an absence of dramatic anticipation (1,12,17). However, it remains unclear whether such classic clinical features of ADCA type 3 are also applicable to SCA6.…”

Section: Discussionmentioning

confidence: 99%

“…Deep tendon reflexes in lower limbs, plantar responses and vibration sense varied with each case (Table 1). Some cases exhibited rapid disease progression (Cases 3,4), severe ataxia (Cases I, 3,4), very early onset age (Case 5 ) and dramatic anticipation (Cases 1,2), which are not classical clinical features of ADCA type 3 in the literature (1,12,17). The clinical features of the representative cases are briefly described as.…”

Section: Clinical Analysis Of Sca6mentioning

confidence: 99%

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Frequency analysis of autosomal dominant cerebellar ataxias in Japanese patients and clinical characterization of spinocerebellar ataxia type 6

et al. 1998

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Using a molecular diagnostic approach, we investigated 101 kindreds with autosomal dominant cerebellar ataxias (ADCAs) from the central Honshu island of Japan, including spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2), Machado‐Joseph disease (MJD), dentatorubral and pallidoluysian atrophy (DRPLA) and spinocerebellar ataxia type 6 (SCA6). In our unselected series, MJD was the most common type of ADCA, accounting for 33.7% followed by DRPLA (19.8%), SCA2 (5.9%) and SCA6 (5.9%). No SCA1 mutations were identified. We analysed the clinical features of six molecular confirmed SCA6 kindreds: in each family, there was an expanded allele in the αdA‐voltage dependent calcium channel comprising between 23 and 25 CAG repeats. The mean age at onset of symptoms was 43 ± 13 years. The clinical features consisted predominantly of cerebellar ataxia, dysarthria and horizontal nystagmus, which was generally consistent with ADCA type 3. However several new clinical features were found in some patients: dramatic anticipation, rapid disease progression, severe ataxia associated with action tremor or action myoclonus, and very early onset, which are not described as the classical features of ADCA type 3.

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“…Algumas famílias com formas descritas como "puras" de ataxia cerebelar (tipo III de Harding) foram relatadas e pode tratar-se geneticamente 2 -253 * 60 , da mesma doença. Em algumas destas famílias, ligação com o sistema HLA no cromossomo 6 3 ou com o marcador D6S89 próximo ao locus SCAl 25 foi excluída.…”

Section: Ataxia Espinocerebelar V (Sca5)unclassified

Ataxias cerebelares hereditárias: do martelo ao gen

Arruda

Teive²

1997

Arq. Neuro-Psiquiatr.

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RESUMO -As heredoataxias constituem grupo complexo de doenças neurodegenerativas hereditárias, para o qual várias formas de classificação clínica e patológica foram propostas com sucesso variável. O desenvolvimento das técnicas de biologia molecular trouxe informações importantes que têm permitido caracterizar geneticamente as ataxias cerebelares hereditárias. O reconhecimento das doenças causadas por expansões de trinucleotídeos abre novo capítulo para a pesquisa sobre outros mecanismos de doenças, como na ataxia de Friedreich e nas várias formas de ataxia cerebelar autossômica dominante(SCAl a SCA7), das quais a doença de MachadoJoseph / SCA3 parece ser a mais comum no nosso meio. A deficiência familial de vitamina E (cromossomo 8q) leva a quadro semelhante ao da ataxia de Friedreich (cromossomo 9p), mas responde à reposição oral de tocoferol. Formas familiais de ataxia periódica com (cromossomo 12p) ou sem (cromossomo 19p) mioquimia foram caracterizadas, a primeira resultado de mutações dos gens de canais de potássio. Os portadores do gen da ataxiateleangiectasia (cromossomo 1 lq) representam 1-3% da população e são suscetíveis aos efeitos oncogênicos da radiação iônica. Sem olvidar da importância da avaliação clínica neurológica, a avaliação genética laboratorial passa a ser valiosa ferramenta para o diagnóstico e aconselhamento genético, além do melhor entendimento da patogênese dessas doenças. PALAVRAS-CHAVE: ataxia cerebelar, doenças cerebelares, trinucleotídeos, genética. Hereditary cerebellar ataxias from neurological hammer to geneticsABSTRACT -The hereditary ataxias comprise a complex group of neurological disorders involving the cerebellum and its connections. Several classifications based on clinical and/or pathological data have been only partially successful. Recent progress in molecular genetics has identified the genic loci of hereditary ataxias and has allowed a more precise diagnosis of distinct genetic diseases. Trinucleotide repeat expansions has been recognized as a mechanism of disease in some autosomal dominant spinocerebellar ataxias (ADCA) (SCA1 to SCA7), including Machado-Joseph disease / SCA3, probably the most common form of ADCA in South Brazil, and Friedreich ataxia (GAA expansion -chromosome 9p). Familial alpha-tocopherol deficiency (chromosome 8q) may have a Friedreich ataxia phenotype and responds to the oral supplementaion with vitamin E. Familial episodic ataxias with (EA1 -chromosome 12p) and without (chromosome 19p -EA2) myokimia were identified, the first one caused by point mutations in the gene encoding the KCNA1 potassium voltage-gated channel. The gene responsible for ataxia-teleangiectasia (chromosome 1 lq) was found to encode a putative DNA binding protein kinase (ATM), related to the cell cycle control. One to 3% of the population are heterozygotic ATM gen carry and pose a higher risk of cancer when exposed to ionizing radiation. Molecular biology has provided us with useful tools to diagnosis and genetic counseling and, hopefully, will provide us with a better under...

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Autosomal Dominant Pure Cerebellar Ataxia

Cited by 12 publications

References 3 publications

Absence of spinocerebellar ataxia type 3/Machado–Joseph disease within ataxic patients in the Czech population

Absence of spinocerebellar ataxia type 3/Machado–Joseph disease within ataxic patients in the Czech population

Frequency analysis of autosomal dominant cerebellar ataxias in Japanese patients and clinical characterization of spinocerebellar ataxia type 6

Ataxias cerebelares hereditárias: do martelo ao gen

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