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Koji Abe - One of the best experts on this subject based on the ideXlab platform.
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spinocerebellar ataxia type 6 cag Trinucleotide Expansion clinical characteristics and sperm analysis
European Journal of Neurology, 1998Co-Authors: Masami Shizuka, Koji Abe, Kazuyuki Mizushima, Mitsunori Watanabe, Koichi Okamoto, Yoshio Ikeda, Mitsuyasu Kanai, T Tsuda, Mikio ShojiAbstract:Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant spinocerebellar degeneration caused by CAG repeat Expansions in the human α1A voltage-dependent calcium channel subunit gene. We analyzed 16 SCA6 patients in 14 unrelated Japanese families, and documented the clinical and molecular properties correlating with the CAG repeat Expansion. Three of them were sporadic. The CAG repeat number of the expanded and normal alleles was 22.7 ± 2.0 (mean ± SD, n = 15) and 13.8 ± 2.0 (n = 15), respectively, and the repeat size of the expanded alleles correlated inversely with age at onset. The patients presented here were clinically characterized by a slowly progressive cerebellar ataxia and nystagmus. In leukocytes, the strict pattern of the peak in the expanded allele on polyacrylamide gel electrophoresis did not show the presence of cell mosaicism in SCA6, in contrast to other Trinucleotide disorders. Moreover, in each patient, the number of CAG repeats in sperm was the same as in leukocytes, and the expanded alleles in sperm indicated uniform peaks as well. In our geographic area, the frequency of SCA6 was as high as MJD, in contrast to the low frequency of other autosomal dominant cerebellar ataxias. Thus, a geographic difference in the frequency of autosomal dominant spinocerebellar ataxias may be present in Japan.
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Analysis of spinocerebellar ataxia type 2 in Gunma Prefecture in Japan: CAG Trinucleotide Expansion and clinical characteristics
Journal of the neurological sciences, 1998Co-Authors: Kazuyuki Mizushima, Masashi Aoki, Koji Abe, Yasuto Itoyama, Mitsunori Watanabe, Masami Shizuka, Koichi Okamoto, Mikio ShojiAbstract:We analyzed 13 patients with spinocerebellar ataxia type 2 (SCA2) in seven unrelated families who live in Gunma Prefecture, Japan (population approx. 2 000 000), and documented the clinical and molecular properties correlated with the CAG repeat Expansion. Twelve of the 13 patients and one presymptomatic female were genetically examined, and the CAG repeat number of the expanded and normal alleles was 40.8±4.8 (mean±S.D., n=13) and 22±0 (n=13), respectively. The repeat size of the expanded alleles was inversely correlated with the patients' age at onset. Paternal anticipation was observed, accompanied by an increase of the CAG repeat size. The patients presented here were clinically characterized by a relatively higher frequency of slow saccades, hyporeflexia, hypotonia, and tremor. A number of peaks in the expanded allele on polyacrylamide gel electrophoresis showed the presence of cell mosaicism in SCA2 as well. In Gunma Prefecture, SCA2, Machado-Joseph disease and spinocerebellar ataxia type 6 are almost equally present and at higher frequencies than spinocerebellar ataxia type 1 and hereditary dentatorubropallidoluysian atrophy, which are rare. Thus, the difference of frequency of autosomal dominant spinocerebellar ataxias may be present in Japan.
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ocular changes in patients with spinocerebellar degeneration and repeated Trinucleotide Expansion of spinocerebellar ataxia type 1 gene
Archives of Ophthalmology, 1997Co-Authors: Toshiaki Abe, Masashi Aoki, Koji Abe, Yasuto Itoyama, Makoto TamaiAbstract:Objective: To examine ocular changes in patients with spinocerebellar degeneration who have repeated Trinucleotide Expansion in the spinocerebellar ataxia type 1 ( SCA1 ) gene. Design: Ophthalmic findings in 6 patients from 3 families whose DNA analysis revealed that they had an expanded allele of the Trinucleotide repeated in the SCA1 gene were compared with those of normal control subjects and other healthy family members. The DNA was extracted from peripheral blood lymphocytes of the neurodegenerative family and normal control subjects. Setting: University medical center. Results: Visual acuity gradually decreased in successive follow-up visits. Color vision and visual fields were gradually affected. Electroretinograms showed mild attenuation of oscillatory potentials. Corneal endothelial cell density was severely decreased from 600 to 1300 cells/mm 2 . These findings were not observed in the normal control subjects, other healthy family members, or other patients with spinocerebellar degeneration who had repeated Trinucleotide Expansion of other genes. Conclusion: To the best of our knowledge, this is the first report describing the association between ocular changes in patients with spinocerebellar degeneration and gene mutation. These ocular changes were considered specific to patients who had the expanded allele of the repeated Trinucleotide in the SCA1 gene.
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Analysis of CAG Trinucleotide Expansion associated with Machado-Joseph disease
Journal of the Neurological Sciences, 1996Co-Authors: Mitsunori Watanabe, Masashi Aoki, Koji Abe, T. Kameya, Mikio Shoji, Jin Kaneko, Masaki Dceda, Masami Ikhizuka, Yoshio Ikeda, Tomomichi IizukaAbstract:Abstract There are currently some types of autosomal dominant cerebellar ataxias such as Machado-Joseph disease (MJD), spinocerebellar ataxia types 1–5 (SCA1-5), or hereditary dentatorubropallidoluysian atrophy. It is very important for these ataxias to be clinically differentiated, but that is sometimes difficult. In particular, the differential diagnosis between MJD and SCA1 is thought to be the most difficult. Recently, both MJD and SCA1 have been proven to be related to Expansions of CAG Trinucleotide in their causative genes. In this study, 20 cases of MJD in 13 unrelated Japanese families were genetically and clinically examined in comparison with 20 cases of age at onset- and duration-matched Japanese SCA1. The CAG repeat number of expanded MJD and SCA1 alleles was 72.2 ± 3.1 (mean ± SD, n = 20) and 47.3 ± 4.4 ( n = 20), respectively, and each repeat size was inversely correlated with age at onset in both MJD and SCA1. The repeat number in leukocytes increased from parents to children with acceleration of age at onset (anticipation) in MJD. In MJD, the number of CAG repeats in the expanded allele was lower in sperm than that of leukocytes, but was more in SCA1. However, the number of peaks in the expanded allele was greater in sperm than in leukocytes in both MJD and SCA1 (increased mosaicism level). MJD was clinically characterized by a relatively higher frequency of ocular signs such as eyelid retraction, bulging eyes, ophthalmoparesis, and nystagmus, spasticity in lower limbs, and sensory and urinary disturbances in contrast to the SCA1 patients except for slow eye movement. These results indicate that the expanded CAG repeat and clinical features are correlated in both MJD and SCA1, and MJD can be differentiated from SCA1 by clinical characteristics mentioned above as well as DNA analysis.
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analysis of spinocerebellar ataxia type 1 sca1 related cag Trinucleotide Expansion in japan
Neurology, 1995Co-Authors: T. Kameya, Masashi Aoki, Koji Abe, M Sahara, M Tobita, Hidehiko Konno, Yasuto ItoyamaAbstract:Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by Expansion of a CAG Trinucleotide repeat. We analyzed CAG repeat Expansion in 25 families in the northeast of Japan with hereditary ataxia of Menzel type. Twenty of 38 patients in 12 families had expanded allele for SCA1. The number of CAG repeats correlated with the age at onset. Although the relationship between anticipation and the number of CAG repeats in successive generations was not ascertainable, there was a tendency to paternal bias for the accelerated age at onset. Study of the number of CAG repeats in various tissues showed no differences in the repeat length in lymphocytes, muscle, or brain; sperm, however, showed an obvious Expansion. This may be a clue to a possible mechanism for the molecular basis of paternal anticipation of the disease. The SCA1 gene was transcribed from both wild and mutated alleles in muscles of affected individuals, but the repeat length was the same for both the muscle cDNA and the lymphocyte genomic DNA. These results suggest that, in the area of Japan where SCA1 is prevalent, 48% of families with spinocerebellar degeneration have SCA1 mutation.
György Fekete - One of the best experts on this subject based on the ideXlab platform.
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study of patterns of inheritance of premature ovarian failure syndrome carrying maternal and paternal premutations
BMC Medical Genetics, 2018Co-Authors: Artur Beke, Henriett Piko, Iren Haltrich, Veronika Karcagi, Janos Rigo, Maria Judit Molnar, György FeketeAbstract:Premature ovarian failure / primary ovarian insufficiency (POF/POI) associated with the mutations of the FMR1 (Fragile-X Mental Retardation 1) gene belongs to the group of the so-called Trinucleotide Expansion diseases. Our aim was to analyse the relationship between the paternally inherited premutation (PIP) and the maternally inherited premutation (MIP) by the examination of the family members of women with POF, carrying the premutation allele confirmed by molecular genetic testing. Molecular genetic testing was performed in the patients of the 1st Department of Obstetrics and Gynecology with suspected premature ovarian failure. First we performed the southern blot analyses and for the certified premutation cases we used the Repeat Primed PCR. Due to POF/POI, a total of 125 patients underwent genetic testing. The FMR1 gene Trinucleotide repeat number was examined in the DNA samples of the patients, and in 15 cases (12%) deviations (CGG repeat number corresponding to premutation or gray zone) were detected. In 6 cases out of the 15 cases the CGG repeat number fell within the range of the so-called gray zone (41–54 CGG repeat) (4.8%, 6/125), and the FMR1 premutation (55–200 CGG repeat) ratio was 7.2% (9/125). In 4 out of the 15 cases we found differences in both alleles, one was a premutation allele, and the other allele showed a repeat number belonging to the gray zone. Out of 15 cases, only maternal inheritance (MIP) was detected in 2 cases, in one case the premutation allele (91 CGG repeat number), while in the other case an allele belonging to the gray zone (41 CGG repeat number) were inherited from their mothers. In 10 out of 15 cases, the patient inherited the premutation allele only from the father (PIP). In 5 out of the 10 cases (50%) the premutation allele was inherited from the father, and the repeat number ranged from 55 to 133. Out of 125 cases, 9 patients had detectable cytogenetic abnormalities (7.2%). The RP-PCR method can be used to define the smaller premutations and the exact CGG number. Due to the quantitative nature of the RP-PCR, it is possible to detect the mosaicism as well.
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Study of patterns of inheritance of premature ovarian failure syndrome carrying maternal and paternal premutations
BMC, 2018Co-Authors: Artur Beke, Henriett Piko, Iren Haltrich, Veronika Karcagi, Janos Rigo, Maria Judit Molnar, György FeketeAbstract:Abstract Background Premature ovarian failure / primary ovarian insufficiency (POF/POI) associated with the mutations of the FMR1 (Fragile-X Mental Retardation 1) gene belongs to the group of the so-called Trinucleotide Expansion diseases. Our aim was to analyse the relationship between the paternally inherited premutation (PIP) and the maternally inherited premutation (MIP) by the examination of the family members of women with POF, carrying the premutation allele confirmed by molecular genetic testing. Methods Molecular genetic testing was performed in the patients of the 1st Department of Obstetrics and Gynecology with suspected premature ovarian failure. First we performed the southern blot analyses and for the certified premutation cases we used the Repeat Primed PCR. Results Due to POF/POI, a total of 125 patients underwent genetic testing. The FMR1 gene Trinucleotide repeat number was examined in the DNA samples of the patients, and in 15 cases (12%) deviations (CGG repeat number corresponding to premutation or gray zone) were detected. In 6 cases out of the 15 cases the CGG repeat number fell within the range of the so-called gray zone (41–54 CGG repeat) (4.8%, 6/125), and the FMR1 premutation (55–200 CGG repeat) ratio was 7.2% (9/125). In 4 out of the 15 cases we found differences in both alleles, one was a premutation allele, and the other allele showed a repeat number belonging to the gray zone. Out of 15 cases, only maternal inheritance (MIP) was detected in 2 cases, in one case the premutation allele (91 CGG repeat number), while in the other case an allele belonging to the gray zone (41 CGG repeat number) were inherited from their mothers. In 10 out of 15 cases, the patient inherited the premutation allele only from the father (PIP). In 5 out of the 10 cases (50%) the premutation allele was inherited from the father, and the repeat number ranged from 55 to 133. Out of 125 cases, 9 patients had detectable cytogenetic abnormalities (7.2%). Conclusions The RP-PCR method can be used to define the smaller premutations and the exact CGG number. Due to the quantitative nature of the RP-PCR, it is possible to detect the mosaicism as well
Masashi Aoki - One of the best experts on this subject based on the ideXlab platform.
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Analysis of spinocerebellar ataxia type 2 in Gunma Prefecture in Japan: CAG Trinucleotide Expansion and clinical characteristics
Journal of the neurological sciences, 1998Co-Authors: Kazuyuki Mizushima, Masashi Aoki, Koji Abe, Yasuto Itoyama, Mitsunori Watanabe, Masami Shizuka, Koichi Okamoto, Mikio ShojiAbstract:We analyzed 13 patients with spinocerebellar ataxia type 2 (SCA2) in seven unrelated families who live in Gunma Prefecture, Japan (population approx. 2 000 000), and documented the clinical and molecular properties correlated with the CAG repeat Expansion. Twelve of the 13 patients and one presymptomatic female were genetically examined, and the CAG repeat number of the expanded and normal alleles was 40.8±4.8 (mean±S.D., n=13) and 22±0 (n=13), respectively. The repeat size of the expanded alleles was inversely correlated with the patients' age at onset. Paternal anticipation was observed, accompanied by an increase of the CAG repeat size. The patients presented here were clinically characterized by a relatively higher frequency of slow saccades, hyporeflexia, hypotonia, and tremor. A number of peaks in the expanded allele on polyacrylamide gel electrophoresis showed the presence of cell mosaicism in SCA2 as well. In Gunma Prefecture, SCA2, Machado-Joseph disease and spinocerebellar ataxia type 6 are almost equally present and at higher frequencies than spinocerebellar ataxia type 1 and hereditary dentatorubropallidoluysian atrophy, which are rare. Thus, the difference of frequency of autosomal dominant spinocerebellar ataxias may be present in Japan.
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ocular changes in patients with spinocerebellar degeneration and repeated Trinucleotide Expansion of spinocerebellar ataxia type 1 gene
Archives of Ophthalmology, 1997Co-Authors: Toshiaki Abe, Masashi Aoki, Koji Abe, Yasuto Itoyama, Makoto TamaiAbstract:Objective: To examine ocular changes in patients with spinocerebellar degeneration who have repeated Trinucleotide Expansion in the spinocerebellar ataxia type 1 ( SCA1 ) gene. Design: Ophthalmic findings in 6 patients from 3 families whose DNA analysis revealed that they had an expanded allele of the Trinucleotide repeated in the SCA1 gene were compared with those of normal control subjects and other healthy family members. The DNA was extracted from peripheral blood lymphocytes of the neurodegenerative family and normal control subjects. Setting: University medical center. Results: Visual acuity gradually decreased in successive follow-up visits. Color vision and visual fields were gradually affected. Electroretinograms showed mild attenuation of oscillatory potentials. Corneal endothelial cell density was severely decreased from 600 to 1300 cells/mm 2 . These findings were not observed in the normal control subjects, other healthy family members, or other patients with spinocerebellar degeneration who had repeated Trinucleotide Expansion of other genes. Conclusion: To the best of our knowledge, this is the first report describing the association between ocular changes in patients with spinocerebellar degeneration and gene mutation. These ocular changes were considered specific to patients who had the expanded allele of the repeated Trinucleotide in the SCA1 gene.
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Analysis of CAG Trinucleotide Expansion associated with Machado-Joseph disease
Journal of the Neurological Sciences, 1996Co-Authors: Mitsunori Watanabe, Masashi Aoki, Koji Abe, T. Kameya, Mikio Shoji, Jin Kaneko, Masaki Dceda, Masami Ikhizuka, Yoshio Ikeda, Tomomichi IizukaAbstract:Abstract There are currently some types of autosomal dominant cerebellar ataxias such as Machado-Joseph disease (MJD), spinocerebellar ataxia types 1–5 (SCA1-5), or hereditary dentatorubropallidoluysian atrophy. It is very important for these ataxias to be clinically differentiated, but that is sometimes difficult. In particular, the differential diagnosis between MJD and SCA1 is thought to be the most difficult. Recently, both MJD and SCA1 have been proven to be related to Expansions of CAG Trinucleotide in their causative genes. In this study, 20 cases of MJD in 13 unrelated Japanese families were genetically and clinically examined in comparison with 20 cases of age at onset- and duration-matched Japanese SCA1. The CAG repeat number of expanded MJD and SCA1 alleles was 72.2 ± 3.1 (mean ± SD, n = 20) and 47.3 ± 4.4 ( n = 20), respectively, and each repeat size was inversely correlated with age at onset in both MJD and SCA1. The repeat number in leukocytes increased from parents to children with acceleration of age at onset (anticipation) in MJD. In MJD, the number of CAG repeats in the expanded allele was lower in sperm than that of leukocytes, but was more in SCA1. However, the number of peaks in the expanded allele was greater in sperm than in leukocytes in both MJD and SCA1 (increased mosaicism level). MJD was clinically characterized by a relatively higher frequency of ocular signs such as eyelid retraction, bulging eyes, ophthalmoparesis, and nystagmus, spasticity in lower limbs, and sensory and urinary disturbances in contrast to the SCA1 patients except for slow eye movement. These results indicate that the expanded CAG repeat and clinical features are correlated in both MJD and SCA1, and MJD can be differentiated from SCA1 by clinical characteristics mentioned above as well as DNA analysis.
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analysis of spinocerebellar ataxia type 1 sca1 related cag Trinucleotide Expansion in japan
Neurology, 1995Co-Authors: T. Kameya, Masashi Aoki, Koji Abe, M Sahara, M Tobita, Hidehiko Konno, Yasuto ItoyamaAbstract:Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by Expansion of a CAG Trinucleotide repeat. We analyzed CAG repeat Expansion in 25 families in the northeast of Japan with hereditary ataxia of Menzel type. Twenty of 38 patients in 12 families had expanded allele for SCA1. The number of CAG repeats correlated with the age at onset. Although the relationship between anticipation and the number of CAG repeats in successive generations was not ascertainable, there was a tendency to paternal bias for the accelerated age at onset. Study of the number of CAG repeats in various tissues showed no differences in the repeat length in lymphocytes, muscle, or brain; sperm, however, showed an obvious Expansion. This may be a clue to a possible mechanism for the molecular basis of paternal anticipation of the disease. The SCA1 gene was transcribed from both wild and mutated alleles in muscles of affected individuals, but the repeat length was the same for both the muscle cDNA and the lymphocyte genomic DNA. These results suggest that, in the area of Japan where SCA1 is prevalent, 48% of families with spinocerebellar degeneration have SCA1 mutation.
Mikio Shoji - One of the best experts on this subject based on the ideXlab platform.
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spinocerebellar ataxia type 6 cag Trinucleotide Expansion clinical characteristics and sperm analysis
European Journal of Neurology, 1998Co-Authors: Masami Shizuka, Koji Abe, Kazuyuki Mizushima, Mitsunori Watanabe, Koichi Okamoto, Yoshio Ikeda, Mitsuyasu Kanai, T Tsuda, Mikio ShojiAbstract:Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant spinocerebellar degeneration caused by CAG repeat Expansions in the human α1A voltage-dependent calcium channel subunit gene. We analyzed 16 SCA6 patients in 14 unrelated Japanese families, and documented the clinical and molecular properties correlating with the CAG repeat Expansion. Three of them were sporadic. The CAG repeat number of the expanded and normal alleles was 22.7 ± 2.0 (mean ± SD, n = 15) and 13.8 ± 2.0 (n = 15), respectively, and the repeat size of the expanded alleles correlated inversely with age at onset. The patients presented here were clinically characterized by a slowly progressive cerebellar ataxia and nystagmus. In leukocytes, the strict pattern of the peak in the expanded allele on polyacrylamide gel electrophoresis did not show the presence of cell mosaicism in SCA6, in contrast to other Trinucleotide disorders. Moreover, in each patient, the number of CAG repeats in sperm was the same as in leukocytes, and the expanded alleles in sperm indicated uniform peaks as well. In our geographic area, the frequency of SCA6 was as high as MJD, in contrast to the low frequency of other autosomal dominant cerebellar ataxias. Thus, a geographic difference in the frequency of autosomal dominant spinocerebellar ataxias may be present in Japan.
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Analysis of spinocerebellar ataxia type 2 in Gunma Prefecture in Japan: CAG Trinucleotide Expansion and clinical characteristics
Journal of the neurological sciences, 1998Co-Authors: Kazuyuki Mizushima, Masashi Aoki, Koji Abe, Yasuto Itoyama, Mitsunori Watanabe, Masami Shizuka, Koichi Okamoto, Mikio ShojiAbstract:We analyzed 13 patients with spinocerebellar ataxia type 2 (SCA2) in seven unrelated families who live in Gunma Prefecture, Japan (population approx. 2 000 000), and documented the clinical and molecular properties correlated with the CAG repeat Expansion. Twelve of the 13 patients and one presymptomatic female were genetically examined, and the CAG repeat number of the expanded and normal alleles was 40.8±4.8 (mean±S.D., n=13) and 22±0 (n=13), respectively. The repeat size of the expanded alleles was inversely correlated with the patients' age at onset. Paternal anticipation was observed, accompanied by an increase of the CAG repeat size. The patients presented here were clinically characterized by a relatively higher frequency of slow saccades, hyporeflexia, hypotonia, and tremor. A number of peaks in the expanded allele on polyacrylamide gel electrophoresis showed the presence of cell mosaicism in SCA2 as well. In Gunma Prefecture, SCA2, Machado-Joseph disease and spinocerebellar ataxia type 6 are almost equally present and at higher frequencies than spinocerebellar ataxia type 1 and hereditary dentatorubropallidoluysian atrophy, which are rare. Thus, the difference of frequency of autosomal dominant spinocerebellar ataxias may be present in Japan.
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Analysis of CAG Trinucleotide Expansion associated with Machado-Joseph disease
Journal of the Neurological Sciences, 1996Co-Authors: Mitsunori Watanabe, Masashi Aoki, Koji Abe, T. Kameya, Mikio Shoji, Jin Kaneko, Masaki Dceda, Masami Ikhizuka, Yoshio Ikeda, Tomomichi IizukaAbstract:Abstract There are currently some types of autosomal dominant cerebellar ataxias such as Machado-Joseph disease (MJD), spinocerebellar ataxia types 1–5 (SCA1-5), or hereditary dentatorubropallidoluysian atrophy. It is very important for these ataxias to be clinically differentiated, but that is sometimes difficult. In particular, the differential diagnosis between MJD and SCA1 is thought to be the most difficult. Recently, both MJD and SCA1 have been proven to be related to Expansions of CAG Trinucleotide in their causative genes. In this study, 20 cases of MJD in 13 unrelated Japanese families were genetically and clinically examined in comparison with 20 cases of age at onset- and duration-matched Japanese SCA1. The CAG repeat number of expanded MJD and SCA1 alleles was 72.2 ± 3.1 (mean ± SD, n = 20) and 47.3 ± 4.4 ( n = 20), respectively, and each repeat size was inversely correlated with age at onset in both MJD and SCA1. The repeat number in leukocytes increased from parents to children with acceleration of age at onset (anticipation) in MJD. In MJD, the number of CAG repeats in the expanded allele was lower in sperm than that of leukocytes, but was more in SCA1. However, the number of peaks in the expanded allele was greater in sperm than in leukocytes in both MJD and SCA1 (increased mosaicism level). MJD was clinically characterized by a relatively higher frequency of ocular signs such as eyelid retraction, bulging eyes, ophthalmoparesis, and nystagmus, spasticity in lower limbs, and sensory and urinary disturbances in contrast to the SCA1 patients except for slow eye movement. These results indicate that the expanded CAG repeat and clinical features are correlated in both MJD and SCA1, and MJD can be differentiated from SCA1 by clinical characteristics mentioned above as well as DNA analysis.
Yasuto Itoyama - One of the best experts on this subject based on the ideXlab platform.
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Analysis of spinocerebellar ataxia type 2 in Gunma Prefecture in Japan: CAG Trinucleotide Expansion and clinical characteristics
Journal of the neurological sciences, 1998Co-Authors: Kazuyuki Mizushima, Masashi Aoki, Koji Abe, Yasuto Itoyama, Mitsunori Watanabe, Masami Shizuka, Koichi Okamoto, Mikio ShojiAbstract:We analyzed 13 patients with spinocerebellar ataxia type 2 (SCA2) in seven unrelated families who live in Gunma Prefecture, Japan (population approx. 2 000 000), and documented the clinical and molecular properties correlated with the CAG repeat Expansion. Twelve of the 13 patients and one presymptomatic female were genetically examined, and the CAG repeat number of the expanded and normal alleles was 40.8±4.8 (mean±S.D., n=13) and 22±0 (n=13), respectively. The repeat size of the expanded alleles was inversely correlated with the patients' age at onset. Paternal anticipation was observed, accompanied by an increase of the CAG repeat size. The patients presented here were clinically characterized by a relatively higher frequency of slow saccades, hyporeflexia, hypotonia, and tremor. A number of peaks in the expanded allele on polyacrylamide gel electrophoresis showed the presence of cell mosaicism in SCA2 as well. In Gunma Prefecture, SCA2, Machado-Joseph disease and spinocerebellar ataxia type 6 are almost equally present and at higher frequencies than spinocerebellar ataxia type 1 and hereditary dentatorubropallidoluysian atrophy, which are rare. Thus, the difference of frequency of autosomal dominant spinocerebellar ataxias may be present in Japan.
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ocular changes in patients with spinocerebellar degeneration and repeated Trinucleotide Expansion of spinocerebellar ataxia type 1 gene
Archives of Ophthalmology, 1997Co-Authors: Toshiaki Abe, Masashi Aoki, Koji Abe, Yasuto Itoyama, Makoto TamaiAbstract:Objective: To examine ocular changes in patients with spinocerebellar degeneration who have repeated Trinucleotide Expansion in the spinocerebellar ataxia type 1 ( SCA1 ) gene. Design: Ophthalmic findings in 6 patients from 3 families whose DNA analysis revealed that they had an expanded allele of the Trinucleotide repeated in the SCA1 gene were compared with those of normal control subjects and other healthy family members. The DNA was extracted from peripheral blood lymphocytes of the neurodegenerative family and normal control subjects. Setting: University medical center. Results: Visual acuity gradually decreased in successive follow-up visits. Color vision and visual fields were gradually affected. Electroretinograms showed mild attenuation of oscillatory potentials. Corneal endothelial cell density was severely decreased from 600 to 1300 cells/mm 2 . These findings were not observed in the normal control subjects, other healthy family members, or other patients with spinocerebellar degeneration who had repeated Trinucleotide Expansion of other genes. Conclusion: To the best of our knowledge, this is the first report describing the association between ocular changes in patients with spinocerebellar degeneration and gene mutation. These ocular changes were considered specific to patients who had the expanded allele of the repeated Trinucleotide in the SCA1 gene.
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analysis of spinocerebellar ataxia type 1 sca1 related cag Trinucleotide Expansion in japan
Neurology, 1995Co-Authors: T. Kameya, Masashi Aoki, Koji Abe, M Sahara, M Tobita, Hidehiko Konno, Yasuto ItoyamaAbstract:Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by Expansion of a CAG Trinucleotide repeat. We analyzed CAG repeat Expansion in 25 families in the northeast of Japan with hereditary ataxia of Menzel type. Twenty of 38 patients in 12 families had expanded allele for SCA1. The number of CAG repeats correlated with the age at onset. Although the relationship between anticipation and the number of CAG repeats in successive generations was not ascertainable, there was a tendency to paternal bias for the accelerated age at onset. Study of the number of CAG repeats in various tissues showed no differences in the repeat length in lymphocytes, muscle, or brain; sperm, however, showed an obvious Expansion. This may be a clue to a possible mechanism for the molecular basis of paternal anticipation of the disease. The SCA1 gene was transcribed from both wild and mutated alleles in muscles of affected individuals, but the repeat length was the same for both the muscle cDNA and the lymphocyte genomic DNA. These results suggest that, in the area of Japan where SCA1 is prevalent, 48% of families with spinocerebellar degeneration have SCA1 mutation.
