並列タイトル等Identification of a novel variant of the RET proto‑oncogene in a novel family with Hirschsprung’s disease
タイトル(掲載誌)Pediatric Surgery International
学位博士(医学)
Doctor of Philosophy in Medical Science
一般注記博士論文全文, 最終試験結果の要旨, 論文審査の要旨, 博士論文要旨
Purpose: Hirschsprung’s disease (HSCR) is a congenital disorder of the enteric nervous system characterized by the absence of ganglion cells in the Auerbach’s and Meissner’s plexuses. Although about 7% of cases are hereditary, the causal mutations have not been completely characterized. We encountered a novel family with inherited HSCR and screened them for causal mutations.Methods: A Japanese family of five female patients and six unaffected individuals was subjected to a whole-exome analysis with a next-generation sequencer.Results: After exome sequencing and the annotation of mutations, we identified co-segregated mutations with sequential filtering steps via a standard protocol. Eight mutations were identified: 2 on chromosome 10 and 6 on chromosome 11. We used pathogenicity prediction tools such as Genomic Evolutionary Rate Profiling, SIFT, and PolyPhen2 to predict the impact of mutations on the protein activity. S922Y, a novel mutation of RET, was identified as a likely causal mutation. In addition, a mutation of rs2435357T, known enhancer of RET located in intron 1 of RET, was detected in this family.Conclusion: The coexistence of RET mutations in both the exon (S922Y) and intron1 (rs2435357T) indicated a risk of HSCR in this family.
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受理日(W3CDTF)2018-11-05T10:48:21+09:00
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