@phdthesis{oai:ir.kagoshima-u.ac.jp:00014407,
 author = {川野, 孝文 and Kawano, Takafumi},
 month = {Oct},
 note = {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.},
 school = {鹿児島大学},
 title = {Identification of a novel variant of the RET proto‑oncogene in a novel family with Hirschsprung’s disease},
 year = {2017},
 yomi = {カワノ, タカフミ}
}