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ID 114920
タイトル別表記
Genetic Alterations in Gorlin Syndrome
著者
Morita, Kei-ichi Tokyo Medical and Dental University
Tanimoto, Kousuke Tokyo Medical and Dental University
Yasukawa, Chisato Tokyo Medical and Dental University
Oikawa, Yu Tokyo Medical and Dental University
Inazawa, Johji Tokyo Medical and Dental University
Omura, Ken Tokyo Medical and Dental University|Tokyo General Hospital
Harada, Hiroyuki Tokyo Medical and Dental University
資料タイプ
学術雑誌論文
抄録
Gorlin syndrome (GS) is an autosomal dominant disorder that predisposes affected individuals to developmental defects and tumorigenesis, and caused mainly by heterozygous germline PTCH1 mutations. Despite exhaustive analysis, PTCH1 mutations are often unidentifiable in some patients; the failure to detect mutations is presumably because of mutations occurred in other causative genes or outside of analyzed regions of PTCH1, or copy number alterations (CNAs). In this study, we subjected a cohort of GS-affected individuals from six unrelated families to next-generation sequencing (NGS) analysis for the combined screening of causative alterations in Hedgehog signaling pathway-related genes. Specific single nucleotide variations (SNVs) of PTCH1 causing inferred amino acid changes were identified in four families (seven affected individuals), whereas CNAs within or around PTCH1 were found in two families in whom possible causative SNVs were not detected. Through a targeted resequencing of all coding exons, as well as simultaneous evaluation of copy number status using the alignment map files obtained via NGS, we found that GS phenotypes could be explained by PTCH1 mutations or deletions in all affected patients. Because it is advisable to evaluate CNAs of candidate causative genes in point mutation-negative cases, NGS methodology appears to be useful for improving molecular diagnosis through the simultaneous detection of both SNVs and CNAs in the targeted genes/regions.
掲載誌名
PLOS ONE
ISSN
19326203
出版者
PLOS
10
11
開始ページ
e0140480
発行日
2015-11-06
権利情報
© 2015 Morita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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言語
eng
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出版社版
部局
医学系