Severity and Progression Rate of Cerebellar Ataxia in 16q-linked Autosomal Dominant Cerebellar Ataxia (16q-ADCA) in the Endemic Nagano Area of Japan

Yoshida, Katsumi; Shimizu, Yoshifusa; Morita, Hiroshi; Okano, Takahiro; Sakai, Haruko; Ohata, Takako; Matsumoto, Naomichi; Nakamura, Katsuya; Tazawa, Ko-ichi; Ohara, Shuichi; Tabata, Ken‐ichi; Inoue, Atsushi; Sato, Shunichi; Shimojima, Yasuhiro; Hattori, Takeshi; Ushiyama, Masao; Ikeda, Shu‐ichi

doi:10.1007/s12311-008-0062-8

Cited by 14 publications

(9 citation statements)

References 30 publications

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“…Furthermore, the repeat size of (TAGAA) n is comparatively uniform within the endemic foci. From the geographical viewpoint, we previously supposed that there were two major foci in the southwest (Ina–Kiso) and east (Saku) areas in Nagano [15], but patients in Ina and Kiso areas are likely to be different from the viewpoint of population genetics because the number of (TAGAA) n repeats and the size of the insertion were obviously different between the two groups.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the frequency of SCA31 in Nagano is much higher than in other areas of Japan [7–11]. We have found that SCA31 families are highly prevalent in particular areas of Nagano, named as Kiso, Ina, and Saku [13–15], see Fig. 2].…”

Section: Introductionmentioning

confidence: 99%

“…We have shown that SCA31 is the most predominant subtype of ADCA in Nagano, which is located in the central, mountainous district of the main island of Japan [13–15], see Fig. 2].…”

Section: Introductionmentioning

confidence: 99%

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Analysis of an insertion mutation in a cohort of 94 patients with spinocerebellar ataxia type 31 from Nagano, Japan

Sakai

Yoshida

Shimizu³

et al. 2010

Neurogenetics

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Spinocerebellar ataxia type 31 (SCA31) is a recently defined subtype of autosomal dominant cerebellar ataxia (ADCA) characterized by adult-onset, pure cerebellar ataxia. The C/T substitution in the 5′-untranslated region of the puratrophin-1 gene (PLEKHG4) or a disease-specific haplotype within the 900-kb SCA31 critical region just upstream of PLEKHG4 has been used for the diagnosis of SCA31. Very recently, a disease-specific insertion containing penta-nucleotide (TGGAA)n repeats has been found in this critical region in SCA31 patients. SCA31 was highly prevalent in Nagano, Japan, where SCA31 accounts for approximately 42% of ADCA families. We screened the insertion in 94 SCA31 patients from 71 families in Nagano. All patients had a 2.6- to 3.7-kb insertion. The size of the insertion was inversely correlated with the age at onset but not associated with the progression rate after onset. (TAGAA)n repeats at the 5′-end of the insertion were variable in number, ranging from 0 (without TAGAA sequence) to 4. The number of (TAGAA)n repeats was inversely correlated to the total size of the insertion. The number of (TAGAA)n repeats was comparatively uniform within patients from the three endemic foci in Nagano. Only one patient, heterozygous for the C/T substitution in PLEKHG4, had the insertions in both alleles; they were approximately 3.0 and 4.3 kb in size. Sequencing and Southern hybridization using biotin-labeled (TGGAA)5 probe strongly indicated that the 3.0-kb insertion, but not the 4.3-kb insertion, contained (TGGAA)n stretch. We also found that 3 of 405 control individuals (0.7%) had the insertions from 1.0 to 3.5 kb in length. They were negative for the C/T substitution in PLEKHG4, and neither of the insertions contained (TGGAA)n stretch at their 5′-end by sequencing. The insertions in normal controls were clearly detected by Southern hybridization using (TAAAA)5 probe, while they were not labeled with (TGGAA)5 or (TAGAA)5 probe. These data indicate that control alleles very rarely have a nonpathogenic large insertion in the SCA31 critical region and that not only the presence of the insertion but also its size is not sufficient evidence for a disease-causing allele. We approve of the view that (TGGAA)n repeats in the insertion are indeed related to the pathogenesis of SCA31, but it remains undetermined whether a large insertion lacking (TGGAA)n is nonpathogenic.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Analysis of an insertion mutation in a cohort of 94 patients with spinocerebellar ataxia type 31 from Nagano, Japan

Sakai

Yoshida

Shimizu³

et al. 2010

Neurogenetics

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“…SCA31 patients tend to show gait instability with or without dysarthria as initial symptoms, more frequent hearing impairments, and a less-persistent gaze-evoked nystagmus in comparison with SCA6 patients. Correlations between SARA, age at examination, and duration of disease in patients with SCA31 and SCA6 suggested that SARA scores increase more rapidly in SCA31 patients than in SCA6 patients, but the diff erence was not signifi cant (Yoshida et al, 2009).…”

Section: Discussionmentioning

confidence: 92%

Clinical characteristics of combined cases of spinocerebellar ataxia types 6 and 31

Ohmori

Hara

Ishikawa

et al. 2015

Journal of Neurogenetics

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This study reports the first family in which spinocerebellar ataxia type 6 (SCA6) and spinocerebellar ataxia type 31 (SCA31) mutations were seen. An index patient first presented to our hospital due to gait and speech disturbances. Subsequent clinical investigation of this patient and her family members revealed consistent pure cerebellar ataxia transmitted in an autosomal-dominant manner. Genetic examination unexpectedly demonstrated that two of the five affected individuals had expansions of SCA6 and SCA31, while two others had SCA31 alone and the remaining had SCA6. Clinical manifestations were more severe in individuals with combined mutations relative to those with single mutation, suggesting that the SCA6 and SCA31 mutations have a cumulative pathogenic effect.

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“…Previous reports described that it was difficult to distinguish SCA6 and SCA31 in clinical situations. There is not much difference except that the onset age of SCA31 is slightly higher than that of SCA6 [4,5].…”

Section: Introductionmentioning

confidence: 82%

Rare frequency of downbeat positioning nystagmus in spinocerebellar ataxia type 31

Yabe

Matsushima

Yoshida

et al. 2015

Journal of the Neurological Sciences

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Spinocerebellar ataxia type 31 (SCA31) and spinocerebellar ataxia type 6 (SCA6) are the most frequent types of spinocerebellar degeneration in Japan. Previous reports described that it was difficult to distinguish SCA6 and SCA31 in clinical situations. There is not much difference except that the onset age of SCA31 is slightly higher than that of SCA6. Therefore we surveyed our medical records retrospectively, and then compared clinical symptoms of SCA6 and SCA31. As previously stated, the onset age of SCA31 is higher than that of SCA6. Gaze-evoked nystagmus is more frequent in SCA6 than in SCA31. The percentage in downbeat positioning nystagmus (DPN) is as high as 63% in SCA6. In contrast, DPN in SCA31 is rare and subtle. Our study suggests that the presence of DPN is an important sign that can differentiate SCA6 from SCA31 clinically.

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Severity and Progression Rate of Cerebellar Ataxia in 16q-linked Autosomal Dominant Cerebellar Ataxia (16q-ADCA) in the Endemic Nagano Area of Japan

Cited by 14 publications

References 30 publications

Analysis of an insertion mutation in a cohort of 94 patients with spinocerebellar ataxia type 31 from Nagano, Japan

Analysis of an insertion mutation in a cohort of 94 patients with spinocerebellar ataxia type 31 from Nagano, Japan

Clinical characteristics of combined cases of spinocerebellar ataxia types 6 and 31

Rare frequency of downbeat positioning nystagmus in spinocerebellar ataxia type 31

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