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Cognitive impairment in a complex family with AAGGG and ACAGG repeat expansions in RFC1 detected by ExpansionHunter Denovo
http://hdl.handle.net/10271/0002000330
http://hdl.handle.net/10271/00020003302fd61810-1c1c-49c4-86a8-9ef69ff8e010
| 名前 / ファイル | ライセンス | アクション |
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論文本文 (1.2 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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| 公開日 | 2025-02-10 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Cognitive impairment in a complex family with AAGGG and ACAGG repeat expansions in RFC1 detected by ExpansionHunter Denovo | |||||||||||
| 言語 | en | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| 資源タイプ | ||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||
| 資源タイプ | doctoral thesis | |||||||||||
| アクセス権 | ||||||||||||
| アクセス権 | open access | |||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||
| その他のタイトル | ||||||||||||
| その他のタイトル | ExpansionHunter Denovoによって検出されたRFC1遺伝子のAAGGGおよびACAGG反復配列伸長を有する複雑な家系における認知機能障害 | |||||||||||
| 著者 |
渡邊, 一樹
× 渡邊, 一樹
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| 書誌情報 |
en : Neurology® Genetics 巻 8, 号 3, p. e682, 発行日 2022-06 |
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| 出版者 | ||||||||||||
| 出版者 | Wolters Kluwer Health | |||||||||||
| 言語 | en | |||||||||||
| 権利 | ||||||||||||
| 言語 | en | |||||||||||
| 権利情報 | (C) 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. | |||||||||||
| 権利 | ||||||||||||
| 言語 | en | |||||||||||
| 権利情報 | This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. | |||||||||||
| 抄録 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | Background and Objectives We investigated the genetic basis and brain metabolism and blood flow of a Japanese family with spinocerebellar degeneration (SCD), with multiple affected members for 3 generations. Methods After excluding DNA repeat expansion (RE) of common SCD genes by fragment analysis, we performed whole-exome sequencing (WES) and whole-genome sequencing (WGS). Homozygosity mapping was performed using these data. REs were investigated with WGS data using ExpansionHunter Denovo and Expansion Hunter. Results WES and WGS were unable to identify likely pathogenic variants, and homozygosity mapping failed to narrow down the locus. However, ExpansionHunter Denovo detected REs in intron 2 of the RFC1 gene and led us to the diagnosis of RFC1-related disorders. Subsequent repeatprimed PCR and Southern blot hybridization analyses revealed that 3 of 6 patients and 1 suspected individual had expansions of AAGGG ((AAGGG)exp) and (ACAGG)exp repeats in a compound heterozygous state and 3 had a homozygous (ACAGG)exp. The patients showed a variety of clinical features, including adult-onset ataxia, sensorimotor neuropathy, head tremor, parkinsonism, dystonia, and cognitive impairment. A comparison of previous reports with those of the family in study suggested that motor neuropathy could be a feature of compound heterozygous patients and biallelic (ACAGG)exp patients. Cognitive function tests showed cognitive impairment with a predominance of frontal lobe dysfunction. Examination of MRI, SPECT, and 18F-fluorodeoxyglucose-PET showed clear cortical damage with frontal lobe predominance in 1 case, but no cerebral damage was evident in the other 2 cases. Discussion Our report shows the usefulness of WGS and RE detection tools for SCD of unknown cause. The studied family with RFC1-related disorders included patients with (ACAGG)exp and (AAGGG)exp in a compound heterozygous state and was characterized by motor neuropathy. Based on the results of cognitive function tests and imaging studies, 1 patient presented with cognitive impairment due to frontal lobe metabolic changes, but there were also patients who presented with cognitive impairment without apparent cerebral metabolic or blood flow, suggesting that other factors are also associated with cognitive impairment. |
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| 言語 | en | |||||||||||
| 学位名 | ||||||||||||
| 学位名 | 博士（医学） | |||||||||||
| 学位の区分 | ||||||||||||
| 内容記述 | doctoral | |||||||||||
| 学位の分野 | ||||||||||||
| 内容記述 | 医学系研究科 | |||||||||||
| 学位授与機関 | ||||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||||
| 学位授与機関識別子 | 13802 | |||||||||||
| 学位授与機関名 | 浜松医科大学 | |||||||||||
| 学位授与機関名 | Hamamatsu University School of Medicine | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2024-03-13 | |||||||||||
| 学位授与番号 | ||||||||||||
| 学位授与番号 | 甲第986号 | |||||||||||
| EISSN | ||||||||||||
| 収録物識別子タイプ | EISSN | |||||||||||
| 収録物識別子 | 2376-7839 | |||||||||||
| PubMed番号 | ||||||||||||
| 関連タイプ | isIdenticalTo | |||||||||||
| 識別子タイプ | PMID | |||||||||||
| 関連識別子 | 36381255 | |||||||||||
| 出版社DOI | ||||||||||||
| 関連タイプ | isIdenticalTo | |||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | https://doi.org/10.1212/NXG.0000000000000682 | |||||||||||
| 著者版フラグ | ||||||||||||
| 出版タイプ | VoR | |||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
