PRIMPOL変異と複数の遺伝子バリアントが表現型に関与すると考えられた慢性進行性外眼筋麻痺症候を呈した家系

• Material Type: 博士論文
• Title: PRIMPOL変異と複数の遺伝子バリアントが表現型に関与すると考えられた慢性進行性外眼筋麻痺症候を呈した家系
• Author/Editor: 笠毛, 渓
• Author Heading: 笠毛, 渓 カサモ, ケイ
• Publication, Distribution, etc.: Elsevier
• Publication Date: 2020
• Publication Date (W3CDTF): 2020
• Alternative Title: A PRIMPOL mutation and variants in multiple genes may contribute to phenotypes in a familial case with chronic progressive external ophthalmoplegia symptoms
• Periodical title: Neuroscience Research
• No. or year of volume/issue: 157
• Volume: 157
• Pages: 58-63
• Degree grantor/type: 鹿児島大学
• Date Granted: 2020-01-28
• Dissertation Number: 甲総研第531号
• Degree Type: 博士(医学); Doctor of Philosophy in Medical Science
• Text Language Code: eng
• Subject Heading: Progressive external ophthalmoplegia; Multiple mitochondrial DNA deletions; Whole-exome sequencing; PRIMPOL
• Target Audience: 一般
• Note (General): 博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨; Chronic progressive external ophthalmoplegia (CPEO) is one of the most common mitochondrial disorders. It is characterized by bilateral, slowly progressing loss of extraocular muscle mobility, orbicularis oculi weakness, ptosis and other neuromuscular symptoms, which are caused by the accumulation of multiple mitochondrial DNA (mtDNA) deletions. Many mutations in different nuclear genes, such as POLG1, POLG2, ANT1, and others, have been described as causing autosomal-inherited CPEO with multiple mtDNA deletions. Most causative genes are involved in mtDNA replication impairment. Here, we report a family with CPEO-like symptoms characterized by multiple muscle mtDNA deletions, ptosis, diabetes, hearing loss, mental retardation, and emotional instability. We performed genetic analyses to identify nuclear gene mutations in the family. DNA from the proband was analyzed by whole-exome sequencing. In addition to possible pathogenic mutations, rare variants were prioritized for gene-functional phenotype interpretation. We found possible pathogenetic mutations in the PRIMPOL, BRCA1, CPT2, and GJB2 genes, and functional polymorphisms in the CARD8, and MEFV genes. Multiple functional polymorphism and possible pathogenic mutations may contribute to mitochondrialdisease-like phenotypes in a composite manner. Kei Kasamo, Masayuki Nakamura, Yoko Daimou, Akira Sano A PRIMPOL mutation and variants in multiple genes may contribute to phenotypes in a familial case with chronic progressive external ophthalmoplegia symptoms Neuroscience Research, 157, 58-63, (2020) DOI:https://doi.org/10.1016/j.neures.2019.07.006
• Format (IMT): application/pdf
• Source: Diss_笠毛_渓_ISK531_2019 （fulltext）; https://ir.kagoshima-u.ac.jp/record/14992/files/Diss_%E7%AC%A0%E6%AF%9B_%E6%B8%93_ISK531_2019.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1016/j.neures.2019.07.006
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 鹿児島大学 : 鹿児島大学リポジトリ