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ID 110418
Title Alternative
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
Author
Hayashi, Yumiko Okayama University
Minami, Mitsuyoshi Matsuyama Red Cross Hospital
Tohyama, Mikiko Ehime University
Yokota, Kenji Nagoya University
Yamada, Daisuke University of Tokyo
Keywords
nevoid basal cell carcinoma syndrome
targeted exome sequencing
chromosomal microarray
PTCH1
Next-generation sequencing
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Journal of Dermatological Science
ISSN
09231811
NCID
AA1075636X
AA11531842
Publisher
Elsevier
Volume
86
Issue
3
Start Page
206
End Page
211
Published Date
2017-03-11
Remark
内容要旨・審査要旨・論文本文の公開。
本論文は, 著者Yoshihiro Matsudateの学位論文として提出され, 学位審査・授与の対象となっている。
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3096号
Diploma Number
甲医第1340号
Granted Date
2017-06-22
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences