Targeted exome sequencing and chromosomal microarray for the molecular diagnosis of nevoid basal cell carcinoma syndrome

• Material Type: 博士論文
• Title: Targeted exome sequencing and chromosomal microarray for the molecular diagnosis of nevoid basal cell carcinoma syndrome
• Author/Editor: Matsudate, Yoshihiro; Naruto, Takuya; Hayashi, Yumiko; Minami, Mitsuyoshi; Tohyama, Mikiko; Yokota, Kenji; Yamada, Daisuke; Imoto, Issei; Kubo, Yoshiaki
• Author Heading: Matsudate, Yoshihiro; Naruto, Takuya; Hayashi, Yumiko; Minami, Mitsuyoshi; Tohyama, Mikiko; Yokota, Kenji; Yamada, Daisuke; Imoto, Issei; Kubo, Yoshiaki
• Publication, Distribution, etc.: Elsevier
• Publication Date: 2017-03-11
• Publication Date (W3CDTF): 2017-03-11
• Alternative Title: ターゲットエクソーム解析および染色体マイクロアレイ解析を用いた母斑性基底細胞癌症候群の遺伝子診断
• Periodical title: Journal of Dermatological Science
• No. or year of volume/issue: 86 3
• Volume: 86
• Issue: 3
• Pages: 206-211
• ISSN (Periodical Title): ISSN : 0923-1811
• Degree grantor/type: 徳島大学
• Date Granted: 2017-06-22
• Dissertation Number: 甲第3096号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: nevoid basal cell carcinoma syndrome; targeted exome sequencing; chromosomal microarray; PTCH1; Next-generation sequencing
• Target Audience: 一般
• Note (General): Background: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder mainly caused by heterozygous mutations of PTCH1. In addition to characteristic clinical features, detection of a mutation in causative genes is reliable for the diagnosis of NBCCS; however, no mutations have been identified in some patients using conventional methods. Objective: To improve the method for the molecular diagnosis of NBCCS. Methods: We performed targeted exome sequencing (TES) analysis using a multi-gene panel, including PTCH1, PTCH2, SUFU, and other sonic hedgehog signaling pathway-related genes, based on next-generation sequencing (NGS) technology in 8 cases in whom possible causative mutations were not detected by previously performed conventional analysis and 2 recent cases of NBCCS. Subsequent analysis of gross deletion within or around PTCH1 detected by TES was performed using chromosomal microarray (CMA). Results: Through TES analysis, specific single nucleotide variants or small indels of PTCH1 causing inferred amino acid changes were identified in 2 novel cases and 2 undiagnosed cases, whereas gross deletions within or around PTCH1, which are validated by CMA, were found in 3 undiagnosed cases. However, no mutations were detected even by TES in 3 cases. Among 3 cases with gross deletions of PTCH1, deletions containing the entire PTCH1 and additional neighboring genes were detected in 2 cases, one of which exhibited atypical clinical features, such as severe mental retardation, likely associated with genes located within the 4.3 Mb deleted region, especially. Conclusion: TES-based simultaneous evaluation of sequences and copy number status in all targeted coding exons by NGS is likely to be more useful for the molecular diagnosis of NBCCS than conventional methods. CMA is recommended as a subsequent analysis for validation and detailedmapping of deleted regions, which may explain the atypical clinical features of NBCCS cases.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1016/j.jdermsci.2017.02.282
• 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): 徳島大学 : 徳島大学機関リポジトリ

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