Phenotype variation correlates with CAG repeat length in SCA2 - A study of 28 Japanese patients

Sasaki, Hidenao; Wakisaka, Akemi; Sanpei, Kazuhiro; Takano, Hiroki; Igarashi, Shuichi; Ikeuchi, Takeshi; Iwabuchi, K; Fukazawa, Toshiyuki; Hamada, Takeshi; Yuasa, Tatsuhiko; Tsuji, Shoji; Tashiro, Kunio

doi:10.1016/s0022-510x(98)00166-x

Cited by 31 publications

(31 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Homozygotes with triplet-repeat expansions of SCA2, SCA3 or SCA6 showed modified or severe phenotypes. [19][20][21][22][23][24] Conversely, homozygotes of SCA3, SCA6, SCA8 and SCA12 did not have severe clinical phenotypes compared with heterozygotes. 19,[25][26][27][28] On the basis of our results, there does not seem to be a strong gene dosage effect in 16q-ADCA.…”

Section: Discussionmentioning

confidence: 94%

Clinical and genetic characterization of 16q-linked autosomal dominant spinocerebellar ataxia in South Kyushu, Japan

et al. 2009

View full text Add to dashboard Cite

16q-ADCA (OMIM no. 117210) is an autosomal dominant spinocerebellar ataxia (AD-SCA) characterized by late-onset pure cerebellar ataxia and À16C4T substitution of the puratrophin-1 gene. Recently, a series of single-nucleotide polymorphisms (haplotype block) were found to be specific to 16q-ADCA. We screened patients with ataxia and found 62 patients, including four homozygotes who carry the C-T substitution of the puratrophin-1 gene. By further analysis of the patients with the haplotype block, we observed a single-founder effect for 16q-ADCA, even in patients who are supposed to be sporadic late cortical cerebellar atrophy (LCCA). We also observed slippage mutations of microsatellite markers, GATA01 and 17msm, in the pedigrees. We compared the clinical course of 16q-ADCA in heterozygotes and homozygotes with the haplotype block and observed no apparent gene dosage effect. 16q-ADCA accounts for 27% of AD-SCAs and is the most frequent AD-SCA in South Kyushu, Japan.

show abstract

Section: Discussionmentioning

confidence: 94%

Clinical and genetic characterization of 16q-linked autosomal dominant spinocerebellar ataxia in South Kyushu, Japan

et al. 2009

View full text Add to dashboard Cite

show abstract

“…[7][8][9] The expanded ATXN2 gene, which causes spinocerebellar ataxia type 2 (SCA2), was found in some families with only or mainly typical parkinsonism. 10,11 Although some parkinsonism clinical signs such as dystonia and tremor have been described in SCA2, dopamine-responsive parkinsonism has been infrequently described in SCA2 (see ref. 12).…”

Section: Introductionmentioning

confidence: 99%

Genetic and clinical analysis in a Chinese parkinsonism-predominant spinocerebellar ataxia type 2 family

Sun

Satake

Zhang³

et al. 2011

J Hum Genet

View full text Add to dashboard Cite

Parkinson's disease is a degenerative central nervous system disorder that often impairs motor skills, speech and other functions. We discovered a large Chinese family showing primarily parkinsonism symptoms with autosomal dominant inheritance. Six affected individuals in the family showed typical parkinsonism symptoms, including pill-rolling tremor. Two other affected individuals showed cerebellar ataxia symptoms. A whole-genome scan using the 50K single nucleotide polymorphism array with three different linkage methods detected two positive regions on chromosome 12q24.1 and 5q13.3. The ATXN2 gene, responsible for spinocerebellar ataxia type 2 (SCA2) was located precisely in the center of the positive region on chromosome 12. Further analysis of SCA2 revealed heterozygous pathological CAG expansions in the family. The affected individuals' symptoms were typical of parkinsonism, but complex. Inverse correlation between CAG repeat size and age of onset is not obvious in this pedigree. This parkinsonism-predominant SCA2 family shared the same disease gene locus with other 'standard' SCA2 families, but it is possible that variations in one or more modifier genes might account for the parkinsonism-predominant SCA2 predisposition observed in this pedigree.

show abstract

“…Another finding about SCA disease is the large variation of the phenotype. SCA2 has been classified by OPCA, and its phenotype seems to be related to the length of CAG repeats (12,13). However there was no difference in the length on CAG repeats or the gene sequence in our siblings.…”

Section: Discussionmentioning

confidence: 54%

Three Spinocerebellar Ataxia Type 2 Siblings with Ataxia, Parkinsonism, and Motor Neuronopathy

et al. 2011

View full text Add to dashboard Cite

Spinocerebellar ataxia type 2 (SCA2) represents a family of dominant neurodegenerative disorders that results from CAG expansion repeat mutations. The phenotype consists of some common features, most notably progressive ataxia. We describe three siblings with SCA2, manifesting parkinsonism and ataxia in the first sibling, juvenile parkinsonism in the second and motor neuronopathy in the third. Genetic examination revealed expansion to 42, 43, and 42 CAG repeats. There was no relationship between the number of repeats and phenotype. The SCA2 gene should be studied in families with heterogeneous neurodegenerative disorders, including motor neuron disease.

show abstract

Phenotype variation correlates with CAG repeat length in SCA2 - A study of 28 Japanese patients

Cited by 31 publications

References 33 publications

Clinical and genetic characterization of 16q-linked autosomal dominant spinocerebellar ataxia in South Kyushu, Japan

Clinical and genetic characterization of 16q-linked autosomal dominant spinocerebellar ataxia in South Kyushu, Japan

Genetic and clinical analysis in a Chinese parkinsonism-predominant spinocerebellar ataxia type 2 family

Three Spinocerebellar Ataxia Type 2 Siblings with Ataxia, Parkinsonism, and Motor Neuronopathy

Contact Info

Product

Resources

About