Analysis of unique mutations in the LPAR6 gene identified in a Japanese family with autosomal recessive woolly hair/hypotrichosis : Establishment of a useful assay system for LPA_6.

• Material Type: 博士論文
• Title: Analysis of unique mutations in the LPAR6 gene identified in a Japanese family with autosomal recessive woolly hair/hypotrichosis : Establishment of a useful assay system for LPA_6.
• Author/Editor: Hayashi, Ryota
• Publication, Distribution, etc.: 新潟大学
• Publication Date: 2017-03-23
• Publication Date (W3CDTF): 2017-03-23
• Alternative Title: Analysis of unique mutations in the LPAR6 gene identified in a Japanese family with autosomal recessive woolly hair/hypotrichosis : Establishment of a useful assay system for LPA_6.; 常染色体劣性縮毛症/乏毛症の日本人家系で同定されたLPAR6遺伝子変異の解析 : 有用なLPA_6アッセイ系の確立
• Degree grantor/type: 新潟大学
• Date Granted: 2017-03-23
• Date Granted (W3CDTF): 2017-03-23
• Dissertation Number: 甲第4259号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第4259号
• Text Language Code: eng
• Subject Heading: Hypotrichosis; LIPH; LPA(6); LPAR6; Woolly hair
• Note (General): BACKGROUND:Woolly hair (WH) is a hair shaft anomaly characterized by tightly-curled hair and is frequently associated with hypotrichosis. Non-syndromic forms of WH can show either autosomal dominant or recessive inheritance. The autosomal recessive form of WH (ARWH) is caused by mutations in either lipase H (LIPH) or lysophosphatidic acid receptor 6 (LPAR6) gene, encoding an LPA-producing enzyme PA-PLA1α and an LPA receptor LPA6, respectively. OBJECTIVE:To define the molecular basis of ARWH/hypotrichosis in a Japanese family.\ METHODS:We performed mutational analysis of candidate genes and a series of expression and in vitro functional analyses, which we improved in this study, to determine the consequences resulting from the mutations identified in the family.\ RESULTS:Novel compound heterozygous LPAR6 mutations were identified in the patient. One was a nonsense mutation c.756T>A (p.Tyr252*); the other was a large insertion mutation within the promoter region of LPAR6. Expression studies detected LPAR6 mRNA only from the c.756T>A allele in the patient's hair follicles, suggesting that the insertion in the other allele disrupted the LPAR6 promoter and thus led to a failure of transcription. Furthermore, an improved LPA6 functional assay developed in this study demonstrated aberrant expression and a subsequent loss of function of the p.Tyr252*-mutant protein. CONCLUSION:Through establishing a useful assay system for LPA6, our results further underscore the crucial roles of LPAR6 in hair follicle development and hair growth in humans at molecular levels.; 学位の種類: 博士（医学）. 報告番号: 甲第4259号. 学位記番号: 新大院博（医）甲第737号. 学位授与年月日: 平成29年3月23日; Journal of Dermatological Science78(3) 197–205; 新大院博（医）甲第737号; 元資料の権利情報 : Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved
• DOI: info:doi/10.1016/j.jdermsci.2015.03.006; https://doi.org/info:doi/10.1016/j.jdermsci.2015.03.006
• Persistent ID (NDL): info:ndljp/pid/10371265; https://dl.ndl.go.jp/pid/10371265
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2017-07-03T04:10:06+09:00
• Date Created (W3CDTF): 2019-08-05
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
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• Periodical Title (URI): http://hdl.handle.net/10191/47590
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp